Deals Shaping The Medical Industry, June 2015

Derived from Strategic Transactions, Informa’s premium source for tracking life sciences deal activity, the Dealmaking column is a survey of recent health care transactions listed by relevant industry segment – In Vitro Diagnostics, Medical Devices, and Pharmaceuticals – and then categorized by type – Acquisition, Alliance, or Financing. This month’s column covers deals announced in May 2015.

IN VITRO DIAGNOSTICS

Alliances

Biohit Oyj

Mekalasi Oy

Mekalasi Oy agreed to distribute four of Biohit Oyj’s Quick Tests in Finland. (May)

Included in the deal are the Heliobacter Pylori UFT300 Quick Test, which determines H. pylori through a blood test; ColonView Quick Test, a fecal occult-based colorectal screening tool; the Lactose Intolerance Quick Test, which tests for lactase activity in a duodenal biopsy sample; and the Celiac Disease Quick Test, a fingertip blood test to measure serum levels of gluten antibodies.

Trillium Diagnostics LLC

Vivione Biosciences Inc.

In a three-year deal, Vivione Biosciences Inc. received marketing, sales, and distribution rights in North America to Trillium Diagnostics LLC's entire biomarker product line. (May)

In January, Vivione entered into a share purchase agreement to acquire Trillium for $15mm ($1.5mm in cash, $4mm in Vivione stock, and up to $9.5mm in earn-outs), but that agreement expired and Vivione is instead getting a North American license to the biomarkers, with the right to obtain exclusivity in this market upon meeting certain sales goals and potentially expand the agreement to other worldwide regions. Trillium has immunoassay platforms for in vitro diagnostic use in the areas of infection/sepsis detection and monitoring/measurement of fetomaternal hemorrhage (FMH). It holds three patents covering software integrated into flow cytometric assays for quantification of neutrophil CD64 (a marker directly associated with infection and sepsis diagnosis) and soluble CD163 (a protein involved in inflammation regulation). It also has research-only products measuring soluble CD206 (associated with M2 type macrophages) and circulating cell free DNA (cfDNA; observed in disease states such as cancer). Trillium's lead product Leuko64, a quantitative test for neutrophil CD64 expression, has IVD certification in the EU and is awaiting FDA approval. The company's IVD offerings for FMH include FMH QuikQuant (fetal RBC antigen detection) and FETALtrol (CE marked for fetal red cell detection). Vivione will have the use of these products--adding to its own RAPID-B assay platform, which it hopes to commercialize for IVD use later this year--to screen and identify bacteria and determine the efficacy of antimicrobial agents. Vivione also recently optioned worldwide rights to a University of Rochester biomarker for use in creating infectious disease diagnostics.

Financings

HTG Molecular Diagnostics Inc.

Tumor profiling firm HTG Molecular Diagnostics Inc. netted $46.5mm through its initial public offering of 3.57mm shares at $14 (the middle of its intended $13-15 range announced last month). (May)

MEDICAL DEVICES

Mergers & Acquisitions

Can-Fite BioPharma Ltd.

Ophthalix Inc.

Improved Vision Systems Ltd.

OphthaliX Inc. (an 82% owned subsidiary of Can-Fite BioPharma Ltd.) signed a nonbinding term sheet to acquire privately held Improved Vision Systems Ltd. (IVS; eye tracking devices that improve vision). (May)

In order to complete the deal, among other conditions OphthaliX must raise financing and up-list its shares on a US national securities exchange (moving from the OTC market where it currently trades; it filed for an IPO in 2013). IVS's CEO Ram Yam would become OphthaliX's CEO (and join the board, along with IVS CTO Danny Oz). The transaction would bring OphthaliX into the device market for the first time. Up until now, the company has focused on its sole asset CF101 (licensed from Can-Fite), an adenosine A3 receptor agonist in Phase II for ophthalmic indications including glaucoma and uveitis (Can-Fite is separately developing the compound in psoriasis and rheumatoid arthritis). IVS's pipeline includes an eye tracking system--attached to TVs and computer and tablet screens--that monitors vision levels and can accordingly modify images shown on the screen. The company is also developing a mobile device in the form of goggles worn by a patient to track eye movement and display high-definition images.

Circassia Pharmaceuticals PLC

Aerocrine AB

In a move that moves it from an immune-focused firm to a competitor in the respiratory market, Circassia Holdings Ltd. bought public Swedish device firm Aerocrine AB for SEK1.78bn ($216.6mm) in cash, or SEK2.55 per share (a 24% premium). (May)

Circassia gains Aerocrine's point-of-care nitric oxide (NO) monitoring devices NIOX MINO and NIOX VERO for assessing airway inflammation in patients with respiratory conditions. Aerocrine itself sells the products in the US and Germany, but offers the devices in 40 international markets via partners including Stallergenes. Circassia is developing allergy therapies it calls SPIREs (Synthetic Peptide Immuno-Regulatory Epitopes). Lead vaccine candidate, Cat-SPIRE, is in Phase III for cat allergies. With the Aerocrine buy, Circassia has an expanded sales force to help it launch Cat-SPIRE once it's approved. For FYE 2014, Aerocrine reported a loss of SEK228.2mm on SEK166.2mm in revenues, and had SEK189mm in cash on hand at the end of Q1 2015. With 25.2%, Novo AS is the company's largest shareholder. Circassia is concurrently acquiring another respiratory firm, Prosonix Ltd., for up to $157mm ($47mm is an earn-out based on UK approval of lead candidate PSX1001 for asthma).

M Pharmaceutical Inc.

Trimtec Biomedical Inc.

Public device firm M Pharmaceutical Inc. bought closely held Trimtec Biomedical Inc. for its neural gastrointestinal stimulator aimed at treating obesity. M Pharma will issue an undisclosed amount of its common shares. (May)

Trimtec holds exclusive global rights to its IP from the University of Calgary. Developed by university professor Dr. Martin Mintchev (who is also M Pharma's president and CEO), Trimtec's stimulator has proven effective when implanted in animal models. (A similar obesity device was approved by the FDA, though it is designed for implantation in the stomach's gastric vagal nerve.) As part of the Trimtec/U. Calgary alliance, M Pharma is obligated to pay $50k up front, patent costs of $157k over a 20-month period, a $10k milestone payment, and 3% sales royalties. Post-acquisition, M Pharma will have three devices in its portfolio. The company has created the eMosquito pseudo-continuous, minimally invasive blood glucose monitor, which is worn like a cuff on the arm and incorporates small needles to draw blood with little or no pain. And earlier this year M Pharma acquired IP from RX Global Capital associated with temporary controllable pseudobezoars.

Alliances

Intramed Handels GMBH

SciBase AB

SciBase AB granted Intramed Handels GMBH exclusive rights to sell its Nevisense melanoma detection device in Austria, with a focus on private dermatologists. (May)

Nevisense (CE-marked and awaiting FDA approval in the US) is an electrical impedance spectroscopy device that gathers and analyzes electrical measurements through the dermis and epidermis. The system is intended to provide physicians with more detailed information about lesions that have definite characteristics of malignant melanoma, prior to a decision to surgically excise. SciBase looks forward to the expanded geographic reach it gains through the new partnership with Intramed. Nevisense is marketed in Belgium by Dermat Medical Supplies; UK by Globe Skincare; and Australia and New Zealand by Equipmed.

Olympus Corp.

Olympus Medical Systems Group

Terumo Corp.

Terumo Medical Corp.

Olympus Corp. agreed to exclusively distribute Terumo Corp.’s Glidewire urologic hydrophilic coated guidewire in the US. (May)

Terumo’s Terumo Medical Corp. division will supply Olympus Medical Systems Group with the device, which will be marketed by the company’s Olympus Urology and Stone Management sales force. Glidewire is used by urologists to advance and track devices during minimally invasive urology procedures including percutaneous nephrolithotomy (removal of kidney stones through an incision in the patient’s back), lithotripsy (using externally-administered shock waves to break up kidney stones), and ureteroscopy (examination of the ureters using a ureteroscope). Glidewire is complementary to Olympus’ own urology offerings which include cystoscopy, ureteroscopy, nephrectomy, and prostatectomy devices.

Financings

Antares Pharma Inc.

Antares Pharma Inc. (injectors and gel-based drug delivery systems) netted $43.2mm through the public sale of 23mm shares (including the overallotment) at $2. (May)

Investment Banks/Advisors: Oppenheimer & Co. Inc.; Piper Jaffray & Co.; Raymond James & Associates Inc.

Corindus Vascular Robotics Inc.

Corindus Vascular Robotics Inc. netted $39.2mm through its initial public offering of 11mm common shares at $3.80 on NYSE. (May)

Investment Banks/Advisors: Cowen & Co. LLC; Stifel Nicolaus & Co. Inc.

EndoChoice Inc.

EndoChoice Holdings Inc. (endoscopic devices) filed for its initial public offering in which it hopes to sell 6.25mm shares between $15-17. (May)

Investment Banks/Advisors: Bank of America Merrill Lynch; JP Morgan & Co.; Stifel Nicolaus & Co. Inc.; William Blair & Co.

Glaukos Corp.

Glaukos Corp. (glaucoma devices) filed for its initial public offering. (May)

Investment Banks/Advisors: Bank of America Merrill Lynch; Cantor Fitzgerald & Co.; Goldman Sachs & Co.; JP Morgan & Co.; William Blair & Co.

HeartWare International Inc.

HeartWare International Inc. (devices for heart failure) raised $69mm through the sale of 1.75% convertible senior notes due 2021. The notes convert to common at a rate of 10 shares per $1k principal amount, or $100 per share. (HeartWare’s stock was averaging $76.64 at the time of the sale.) (May)

Viveve Medical Inc.

Women's health device firm Viveve Medical Inc. netted $11mm through the sale of 32.4mm shares at $0.37 (a slight discount) to Stonepine Capital (lead) and company management, along with existing investors and affiliates including Alta Bioequities, 5AM Ventures, and 5AM Co-Investors. Stonepine gets an option to designate a board member. Proceeds will help the company pursue market launch of its Viveve System for vaginal laxity. CRT Capital was the placement agent. (May)

Investment Banks/Advisors: CRT Capital Group LLC

PHARMACEUTICALS

Mergers & Acquisitions

Alexion Pharmaceuticals Inc.

Synageva BioPharma Corp.

Alexion Pharmaceuticals Inc. is paying $8.6bn--$115 in cash and 0.6581 shares of its own stock (worth $115.42 each)--for public biotech Synageva BioPharma Corp. (May)

Synageva’s lead program, Kanuma (sebelipase alfa) for lysosomal acid lipase (LAL) deficiency, is currently under regulatory review in the US, Europe, and Mexico with launches expected this year. Next in the pipeline is fast track-designated SBC103, a Phase I/II enzyme replacement therapy for mucopolysaccharidosis IIIB (MPS IIIB or Sanfilippo B syndrome); trial results are expected in H2 2015. Synageva is also working on preclinical SBC105 for rare disorders of calcification, plus various preclinical bio-superior candidates. Alexion’s rare disease portfolio is led by Soliris (eculizumab) for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). The drug was launched in 2007 and generated over $2bn in revenues for 2014. The company is anticipating the approval of Strensiq (asfotase alfa; gained through Alexion’s late-2011 purchase of Enobia) for the rare and serious genetic metabolic disease hypophosphatasia. Post-transaction, Alexion will have eight clinical-stage candidates for eleven indications. Alexion recently licensed rights from Blueprint Medicines to candidates selectively targeting an activated kinase to treat a rare genetic disease. And a few months prior, it penned a drug discovery deal with X-Chem focused on ultra-rare diseases. Synageva kicked off 2015 netting $268.4mm through a follow-on offering. For FYE 2014, Synageva reported a $192.6m net loss on $6.5mm in revenues, and had $98.6mm in cash on hand at the end of Q1 2015. Investment Banks/Advisors: JP Morgan & Co.; Lazard LLC (Alexion Pharmaceuticals Inc.); Goldman Sachs & Co. (Synageva BioPharma Corp.)

Circassia Pharmaceuticals PLC

Prosonix Ltd.

As a means of entry into the respiratory arena, Circassia Holdings Ltd. is paying £70mm ($110mm) up front for nine-year-old pubic respiratory therapeutics developer Prosonix Ltd. Circassia will also hand over up to £30mm should Prosonix's lead asthma candidate PSX1001 receive UK approval before the end of 2017; the amount will drop to £15mm if authorization is obtained after December 31, 2016, and no money will be paid if the product fails to get approval by December 31, 2017. (May)

PSX1001 is partnered under a 2014 deal with Mylan, which has co-promotion rights in various countries worldwide. The candidate is a particle-engineered formulation of GlaxoSmithKline PLC’s inhaled corticosteroid fluticasone Flixotide and is delivered via a pressurized metered-dose inhaler (pMDI). Prosonix's PSX1050, also being co-promoted by GSK, is a version of the Big Pharma's Flovent and is similar to PSX1001 but has a dose counter on the pMDI. Another late-stage asset, PX1439, is a particle-engineered version of salmeterol xinafoate, the active ingredient of GSK’s Serevent for asthma and chronic obstructive pulmonary disease. Prosonix is also working on inhaled dual and triple combination therapies for respiratory diseases using its Multi-component Particle (MCP) platform. Prosonix is based at the Oxford Science Park, where Circassia is also housed. The company is backed by investors including Ventech (holds a 16% stake), Gilde Healthcare Partners (16%), GIMV (13.7%), and Entrepreneurs Fund (12.7%). For FYE 2014, Prosonix generated £10.4mm in sales. On the same day it bought Prosonix, Circassia paid £13.7mm in cash for public Swedish firm Aerocrine AB, which sells two respiratory monitoring devices. Until now, Circassia had been exclusively working on allergy treatments. Lead vaccine candidate, Cat-SPIRE, is in Phase III for cat allergies, and the company also has therapies in Phase IIb for ragweed, grass, and house dust mite allergies.

Endo International PLC

Qualitest Pharmaceuticals

Par Pharmaceutical Holdings Inc.

In its biggest takeover to date, Endo International PLC acquired privately held Par Pharmaceutical for $8bn, including assumed debt. Endo will issue 18mm shares (worth $1.5bn) and pay $6.5bn in cash. (May)

Par was owned by private equity firm TPG, which acquired the drug maker--then a publicly traded company--in 2012 for $2bn. Less than three years later, however, TPG decided that it might realize more value from Par in the public markets, and Par filed for an IPO this past March. Instead, TPG will now sell Par to Endo for four times what it paid in 2012. The current transaction represents a victory for Endo, which just a few months ago lost out on buying GI drug company Salix Pharmaceuticals (in a deal that would have been worth $11bn) to Valeant Pharmaceuticals. With Par (and its existing Qualitest division), Endo is now the fifth-leading generics company in the US behind Teva, Mylan (which Teva is trying to buy), Actavis, and Sandoz. The combined Endo/Par is estimated to have 2014 pro forma revenues of $4.2bn. Par was founded in 1978 and divides its operations among generics, specialty branded drugs (Nascobal and Megace ES), and branded and generic injectable pharmaceuticals. The company has 100 products in its portfolio and more than 200 ANDAs in the pipeline, including assets gained over the recent years in acquisitions of Anchen Pharmaceuticals, Edict Pharmaceuticals (now Par Formulations Pvt. Ltd.), and JHP Pharmaceuticals. Once Endo's acquisition closes, Par's CEO Paul Campanelli will lead the combined firm's generics business. According to Par's S-1 filing, the company had a 2014 net loss of $106mm on net product sales of $1.3bn. Investment Banks/Advisors: JP Morgan & Co. (Par Pharmaceutical Holdings Inc.); Barclays Bank PLC; Deutsche Bank AG; Houlihan Lokey Inc. (Endo International PLC)

Fosun International Ltd.

Shanghai Fosun Pharmaceutical Group Co. Ltd.

WuXi PharmaTech Inc.

Ambrx Inc.

After withdrawing an IPO about a year ago, private bio-conjugates developer Ambrx Inc. found another exit--it will be acquired by a consortium consisting of entities affiliated with Shanghai Fosun Pharmaceutical Group Co. Ltd., HOPU Investments, China Everbright Ltd.'s CEL Healthcare Fund, and WuXi PharmaTech Inc. (May)

Ambrx pulled back from an IPO in June 2014 because of poor market conditions. Under the new ownership structure, both Fosun and WuXi are expected to access Ambrx's biologics capabilities, while Ambrx will gain broader exposure in China. Founded in 2003, Ambrx specializes in conjugation technologies that produce optimized peptides, proteins, and antibodies that retain their potency but may be dosed less frequently. The company's Protein Medicinal Chemistry platform creates bio-conjugates, including bispecific antibodies and antibody-drug conjugates, via site-specific conjugation using proprietary linkers and payloads, or by the introduction of non-native amino acids. Ambrx has partnered with almost all of the major pharmacos, most recently with Bristol-Myers Squibb, Astellas, and Merck & Co. In addition, Ambrx already has a relationship with one of its buyers, WuXi Pharma, which is providing preclinical and clinical development and manufacturing services as part of Ambrx's license agreement with Zhejiang Medicine for Ambrx's lead preclinical ADC ARX788 for Her2-positive breast cancer. ARX788 is expected to enter Phase I later this year. Ambrx's pipeline also contains multiple other programs including ones in oncology, diabetes, weight management, and heart failure. The biotech has raised $101mm in venture financing to date, and its backers include Apposite, Tavistock Life Sciences, Maverick Capital, 5AM Ventures, and Roche Venture Fund. Investment Banks/Advisors: BMO Financial Group (Ambrx Inc.)

Gilead Sciences Inc.

EpiTherapeutics APS

Gilead Sciences Inc. paid $65mm cash to acquire privately held epigenetics company EpiTherapeutics APS. (May)

EpiTherapeutics was established in 2008 by University of Copenhagen's Biotech Research & Innovation Centre researchers to develop therapies based on enzymes involved in transcription regulation in cancer. The company has a pipeline of preclinical small-molecule histone demethylase inhibitors for a variety of tumor types, which Gilead says is highly complementary to its own projects in development. EpiTherapeutics raised over $30mm in seed and Series A funding from investors including Novo Seeds, SEED Capital Denmark, MS Ventures, and Lundbeckfond Emerge.

Juno Therapeutics Inc.

Stage Cell Therapeutics GMBH

Juno Therapeutics Inc. paid €52mm ($59mm) in cash and issued 486k of its shares (valued at €20mm) to acquire the 95% of German biotech Juno Therapeutics GMBH that it didn’t already down. Stage Cell will operate as a wholly owned subsidiary, and will be renamed Juno Therapeutics GMBH. (May)

Through the acquisition (which builds on a relationship that began in 2014, at which time Juno had taken a 5% stake in the company), Juno gets access to Stage’s cell selection and activation technologies. The platforms, based on reversible reagents that allow for isolation and expansion of T-cells during manufacturing, enhance Juno’s own T-cell manufacturing capabilities pertaining to next-generation chimeric antigen receptor (CAR) and T-cell receptor (TCR) therapies. In addition to the up-front money, Juno could pay up to €135mm in earn-outs related to development and sales milestones for novel reagents (€40mm), advanced automation technology (€65mm), and Stage’s existing pipeline (€30mm).

Perrigo Co. PLC

Patheon Inc.

Perrigo Co. PLC acquired the Mexican manufacturing operations of Patheon Inc. for $34mm in cash. The acquisition will be immediately accretive to 2015 adjusted earnings per share, will further strengthen Perrigo's supply chain with the addition of softgel manufacturing technology, and will broaden the company's presence, brand, and customer network in Mexico. (May)

Perrigo spurned multiple recent takeover bids by Rx generics firm Mylan NV. The Patheon deal further boosts Perrigo's value as an acquisition target, as the firm continues integrating Omega Pharma’s operations and managing its OTC private label business.

Pfizer Inc.

AM-Pharma BV

Pfizer Inc. paid $87.5mm in cash for a minority stake in private Dutch firm AM-Pharma BV. The payment also gives Pfizer an exclusive option to buy AM-Pharma at a later date. (May)

The Big Pharma will pay up to another $512.5mm upon option exercise and product launch milestones. AM-Pharma will distribute the up-front fee directly to shareholders. The option is exercisable upon completion of AM-Pharma's Phase II trial of its recombinant alkaline phosphatase (recAP) in acute kidney injury (AKI) related to sepsis; results from the current Phase II study are expected during H2 2016. There are currently no approved therapeutics for the condition. The company is also developing an oral version of the candidate for ulcerative colitis. AM-Pharma has raised $82mm to date in financing.

PlasmaTech Biopharmaceuticals Inc.

Abeona Therapeutics LLC

Just five months after going public on Nasdaq, Abeona Therapeutics Inc. bought closely held Abeona Therapeutics LLC for $13.8mm in stock (4mm shares issued) plus up to $9mm (in cash or stock) for performance-based earn-outs. (May)

Post-transaction, Abeona’s CEO will take the helm of the merged entity. PlasmaTech is looking to create a rare disease-focused gene and cell therapeutics company. Two-year-old Abeona is working on compounds for lysosomal storage diseases and brings to the table its adeno-associated virus (AAV)-based therapies for Sanfilippo syndrome (mucopolysaccharidosis (MPS) types IIIA and IIIB), a disease caused by the body's inability to break down certain sugars, leading to progressive muscular and cognitive deterioration. Intravenous ABX102 (for MPS IIIA) and ABX101 (MPS IIIB) are currently in preclinical studies; Phase I/II trials are expected to commence later this year. They are the only MPS therapies to demonstrate cognitive, muscular, and survival benefits in animal models, and have received both orphan drug and rare pediatric disease designations. The company’s candidates incorporate IP licensed from Nationwide Children's Hospital. Abeona raised over $4mm in seed and Series A funding from various Sanfilippo syndrome-focused institutions. PlasmaTech is working on compounds for inherited COPD (alpha-1 antitrypsin deficiency (AATD)). Concurrent with the M&A announcement, PlasmaTech raised $10mm via a private placement.

Torrent Pharmaceuticals Ltd.

Zyg Pharma Pvt. Ltd.

Torrent Pharmaceuticals Ltd. acquired fellow Indian firm, private dermatology drug manufacturer Zyg Pharma Pvt. Ltd. (May)

In February 2015, rumors surfaced that Zyg was up for sale by its owner, the Encore Group. While the deal value wasn't disclosed, an MP Advisors analyst suggested Zyg could grab a 15-18x EBIDTA multiple. Zyg, established in 1987, makes skin medications, including APIs and finished formulations delivered as creams, ointments, gels, lotions, and other routes. In addition to dermatological products, Zyg also produces antibacterial and antifungal treatments, and offers contract manufacturing services. The company runs an FDA- and Therapeutic Goods Administration-approved manufacturing facility in Pithampur, giving Torrent a fourth-such manufacturing plant in India. Torrent believes Zyg's assets will help it expand into a new therapeutic area--dermatology--especially in developed markets such as the US and Europe. The current deal builds off of Torrent's acquisition in 2013 of Elder Pharmaceuticals' branded formulations business, covering women's health, pain management, wound care, and nutraceuticals. Torrent also recently acquired generic minocycline, an antibacterial drug (that also treats acne), from Ranbaxy, which was required to divest the product as a condition of its merger with Sun Pharmaceutical.

Alliances

Ablynx NV

Sanofi

Genzyme Corp.

Ablynx NV and Sanofi’s Genzyme Corp. teamed up to exclusively research treatments for multiple sclerosis that focus on neuroprotection and CNS repair. (May)

The partners will investigate Nanobodies (therapeutic proteins based on single-domain antibody fragments and containing properties of heavy chain antibodies) that have already been generated by Ablynx against a specific target that plays a role in MS. Genzyme paid an exclusivity fee, and can perform in vitro and in vivo research with Ablynx’s Nanobodies for MS. It also gets an option to enter into a license agreement. Ablynx adds Genzyme to an impressive list of Nanobody partners, including Abbvie, Merck Serono, Boehringer Ingelheim, and Novartis.

Achillion Pharmaceuticals Inc.

Johnson & Johnson

Janssen Pharmaceuticals Inc.

Achillion Pharmaceuticals Inc. licensed Janssen Pharmaceuticals Inc. exclusive worldwide rights to develop and commercialize hepatitis C compounds including ACH3102, ACH3422, and sovaprevir (ACH1625). (May)

Achillion stands to receive up to $905mm in development, regulatory, and sales milestones, plus tiered royalties ranging from the mid-teens to low-twenties (Strategic Transactions assumes 15-23%). Janssen will pay for all costs relating to development and commercial activities. Janssen will focus on developing an oral short-duration, pan-genotypic HCV therapy, initially working on Achillion's fast-tracked Phase II nonstructural protein 5A (NS5A) inhibitor ACH3102 together with Janssen's NS3/4A HCV protease inhibitor simeprevir (the firm's only marketed HCV drug) and the licensed Phase I NS5B polymerase inhibitor ACH3422. Janssen may also choose to study Achillion's Phase II HCV nonstructural protein 3 inhibitor sovaprevir. Achillion's candidates will join Janssen's HCV pipeline, consisting of compounds gained through its September 2014 acquisition of Alios BioPharma--Phase I AL335 and preclinical AL516. Concurrent with the agreement, Johnson & Johnson Development Corp. made a $225mm equity investment in Achillion (about 18.4mm new unregistered shares at $12.15 each). Investment Banks/Advisors: Centerview Partners LLC; Leerink Partners LLC (Achillion Pharmaceuticals Inc.)

Adimab LLC

Celgene Corp.

Two years after agreeing to generate antibodies for Celgene Corp., Adimab LLC penned a second agreement with the biotech, this time for the generation of IgGs against multiple targets. (May)

This time around, Adimab will generate novel common light chain libraries with Celgene and use its proprietary platform to generate IgGs. Adimab can then use the libraries to discover and optimize fully human antibodies, to which Celgene has an option to exclusively license. The two-year term of the deal can be extended for an additional two years. Celgene paid money up front and will hand over license fees, milestones, and royalties.

Antisense Therapeutics Ltd.

Cortendo AB

Strongbridge Biopharma PLC licensed exclusive global rights (excluding Australia and New Zealand) to develop and commercialize Antisense Therapeutics Ltd.'s Phase II antisense compound ATL1103 for endocrinology applications such as acromegaly. (May)

Cortendo will pay $3mm in cash up front and make a $2mm equity investment in Antisense Therapeutics. It could also shell out up to $105mm in development and commercial milestones, plus sales royalties. Cortendo is responsible for funding all development, regulatory, and manufacturing costs of ATL1103, an insulin-like growth factor antagonist. ATL1103 is the product of a late-2001 deal with Isis in which Antisense got rights to the GeneTrove gene functionalization platform to select and assess new antisense compounds for various diseases. Antisense will now focus on another Phase II compound, ATL1102, which is in development for multiple sclerosis, as well as work on ATL1103 in ex-endocrinology indications for which the company retains full global rights and may use all Cortendo-generated data. Cortendo concurrently received rights to another Phase II acromegaly candidate, somatoprim (DG3173), from Aspireo Pharmaceuticals.

AOP Orphan Pharmaceuticals AG

Cardiome Pharma Corp.

AOP Orphan Pharmaceuticals AG licensed Cardiome Pharma Corp. rights to commercialize its cardiovascular drugs Esmocard (esmolol hydrochloride) and Esmocard LYO in Italy, France, Spain, and Belgium. (May)

Esmocard is available as 10mg/10ml solution for injection, while Esmocard LYO is sold in 2500mg powder concentrate for solution for infusion. The drugs are approved for supraventricular tachycardia and the rapid control of the ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or cases in which where short-term control of the ventricular rate with a short-acting agent is suitable. This is the second partnership between the firms; in 2013, AOP Orphan granted Cardiome rights to sell its Brinavess (vernakalant) atrial fibrillation therapy in certain European territories.

Arena Pharmaceuticals Inc.

Arena Pharmaceuticals GMBH

Roivant Sciences Ltd.

Axovant Sciences Ltd.

Roivant Sciences Ltd. received exclusive global development and commercialization rights to Arena Pharmaceuticals GMBH's serotonin 5-HT2A inverse agonist nelotanserin (formerly APD125). (May)

Roivant pays $4mm up front, $41.5mm in development and regulatory milestones, a one-time $60mm sales milestone, and 15% royalties. Arena will manufacture the clinical supply and finished product. Roivant plans to study nelotanserin in Phase III for behavioral and neuropsychiatric disturbances in dementia patients. Arena had tested the candidate in insomnia as far as Phase II, but the company suspended trials in 2008 because the compound didn't reach its primary and secondary endpoints. While not specified, it's assumed that Roivant's wholly owned subsidiary Axovant Sciences Ltd. will advance nelotanserin's development. Axovant is in charge of Roivant's neurology assets, focused on the cognitive, behavioral, and functional components of dementia. Axovant's pipeline currently only contains RVT101, a Phase II selective 5-HT6 antagonist for mild-to-moderate Alzheimer's disease. Axovant, which just filed for an IPO, acquired RVT101 from GSK in 2014.

Ariad Pharmaceuticals Inc.

Gen Ilac ve Saglik Urunleri

Ariad Pharmaceuticals Inc. granted Gen Ilac ve Saglik Urunleri exclusive rights to sell Iclusig (ponatinib) in Turkey for Philadelphia-positive (Ph+) leukemia. (May)

While Gen Ilac distributes the drug as an investigational product on a named-patient basis, Ariad has the option to file for marketing authorization in Turkey; once authorization is received and Iclusig is approved in the territory, Gen Ilac will exclusively market it there. Iclusiq targets the BCR-ABL tyrosine kinase, which is expressed in chronic myeloid leukemia and Ph+ leukemia. The deal with Gen Ilac further expands Ariad’s global reach for the product; late last year, Otsuka paid $77.5mm up front for rights to sell it in Asia. Rights have also been assigned to other partners for Central/Eastern European countries, Israel, and Australia.

Aspen Pharmacare Holdings Ltd.

Endo International PLC

Litha Healthcare Group Ltd.

For $130mm, Aspen Pharmacare Holdings Ltd. sold a group of its branded and generic injectable products marketed in South Africa, as well as drug candidates, to Litha Healthcare Group Ltd. (majority owned by Endo International PLC's Paladin Labs Inc.). (May)

The deal potentially puts Endo closer toward its goal of realizing 25% of its long-term revenues from international business. The acquired assets include 60 drugs in pain, infectious disease, cardiovascular, and other areas, as well as nearly 70 development programs in various phases for cancer, infections, and cardiovascular and respiratory diseases, expected to launch in the next several years. For FYE June 30, 2015, the marketed products recorded $28mm in revenue and $13mm in profit. Endo expects the new medicines to increase Litha's pro-forma revenues by 30% and pro-forma pharmaceutical product revenues by 60%. Through in-licensing deals Paladin has set up with multiple partners including Vyrix, Allergy Therapeutics, and Apeiron, plus its stake in Litha, Endo already has exposure in South Africa. In the last couple years, Endo and Paladin have also expanded in the other emerging market of Mexico, acquiring Grupo Farmaceutico Somar and Ativa Pharma (now Laboratorios Paladin SA de CV). Investment Banks/Advisors: Investec Bank PLC (Aspen Pharmacare Holdings Ltd.)

Aspireo Pharmaceuticals Ltd.

Cortendo AB

Strongbridge Biopharma PLC acquired Aspireo Pharmaceuticals Ltd.’s Phase II somatoprim (DG3173). (May)

Cortendo will issue Aspireo $30 million in equity for DG3173, a somatostatin receptor agonist for treating acromegaly, neuroendocrine and gastroenteropancreatic tumors, Cushing’s disease, and diabetic retinopathy. The compound will join Cortendo's pipeline, which is led by Phase III COR003 for Cushing’s. Concurrently, Cortendo raised $33.2mm in a financing round in which Aspireo's sole backer TVM Capital contributed $4.25mm, and also licensed exclusive global rights (excluding Australia and New Zealand) to Antisense Therapeutics Ltd.'s Phase II antisense compound ATL1103, which is also in development for acromegaly.

Astellas Pharma Inc.

Cyclenium Pharma Inc.

In a two-year deal, Cyclenium Pharma Inc. and Astellas Pharma Inc. seek to identify and develop macrocyclic therapies for undisclosed indications. (May)

Cyclenium will contribute its QUEST Library of next-generation synthetic small-molecule macrocycles and optimization expertise to identify candidates against various Astellas targets. Using its CMRT (Customized Macrocycles for Recognition of Topologies) technology, Cyclenium creates compounds that are advantageous over typical heterocyclic small molecules because they are effective against challenging pharmacological targets, offer an alternative to biological drugs (antibodies, proteins, peptides, oligonucleotides), and can penetrate the blood-brain barrier. The company will handle all medicinal chemistry activities from hit validation to preclinical candidate selection, and Astellas will characterize the biological and pharmacological properties of the compounds and perform all preclinical and clinical development. Astellas will pay Cyclenium an undisclosed up-front fee and research funding.

Atossa Genetics Inc.

Besins Healthcare SA

Besins Healthcare SA granted Atossa Genetics Inc. exclusive global rights to develop and sell its patented afimoxifene gel (4-hydroxytamoxifen) for the treatment and prevention of hyperplasia of the breast. (May)

The deal does not include an up-front payment or milestones related to the primary indication, but Besins will pay 8-9% sales royalties during the first 15 years it commercializes the resulting product. Breast hyperplasia is a condition involving an overgrowth of cells that line the ducts or lobules in the breast. It is typically benign (though in some cases can be precancerous), and can cause pain or discomfort to the patient. Besins’ gel (in Phase II trials) transdermally delivers afimoxifene (an active metabolite of the breast cancer drug tamoxifen) directly to the breast. Atossa is focused on improving breast health through its planned three-step approach: using its patented device to collect nipple aspirate fluid, diagnosing hyperplasia using its lab tests, and now potentially treating the condition with the in-licensed gel, once development is complete. Atossa will set up a manufacturing source for clinical supply and conduct its own Phase II studies, with access to Besins' preclinical and clinical trials and data. In addition to the hyperplasia rights, the company also gets nonexclusive rights to develop the gel for breast cancer and other breast conditions. Milestones for the additional indications include $5mm for the exclusive right to review, access, and refer to Besins’ IND, and $20mm when Atossa begins Phase III trials for each additional therapy area. If Atossa decides to sub-license, Besins gets right of first refusal to sell the afimoxifene gel on a country-by-country basis.

Baxter International Inc.

Baxter BioScience

Sigma-Tau Finanziaria SPA

Baxter International Inc. paid $900mm cash to buy the Oncaspar (pegaspargase) portfolio from Sigma-Tau Finanziaria SPA. Baxter’s Baxalta Inc. division (soon to become the independent publicly traded Baxalta Inc.) will hold rights to the products. (May)

Oncaspar is marketed in the US, Germany, Poland, and other countries to treat acute lymphoblastic leukemia (ALL) as part of a multi-chemo regimen. The product brings in about $100mm in annual sales and will be added to Baxter BioSciences’ offerings in the rare and orphan disease spaces. (The company sells critical care, pulmonology, antibody, and hemophilia therapies, along with vaccines and biosurgery products. The hemophilia assets bring about half of the division’s sales ($3bn).) In addition to the marketed version, Baxter plans to continue developing a lyophilized formulation of Oncaspar in an effort to enhance product stability, and intends to pursue additional indications including acute myeloid leukemia. Lastly, the company gets the related preclinical candidate calaspargase pegol, also for the treatment of ALL but with an increased shelf life for reduced dosing.

Bayer AG

Bayer Korea Ltd.

Dong-A Pharmaceutical Co. Ltd.

Dong-A Pharmaceutical Co. Ltd. acquired four OTC contraceptives from Bayer Korea Ltd. The transaction included legal rights on Korean and English trademarks, manufacturing methods, production know-how, sales rights, and approval data. (May)

Dong-A now owns Myvlar (ethinyl estradiol/gestodene), Meliane (ethinyl estradiol/gestodene), Minivlar (ethinyl estradiol/levonorgestrel), and Triquilar (ethinyl estradiol/levonorgestrel), which together achieved $7.8mm in 2013 revenue and held 39% of the South Korean contraceptives market, still behind the leader in that category, Merck & Co.'s Mercilon (desogestrel/ethinyl estradiol) at 43%. Incidentally, Mercilon would be part of Bayer's acquisition of Merck's OTC operations, announced in May 2014. South Korea's Fair Trade Commission had raised anti-trust concerns over Bayer's potential to inflate prices and deter competition as a result of the Merck acquisition. Initially, the FTC stated the Bayer still needed to sell Mercilon to a third party to ensure the Korean part of the Merck deal goes through, even following the sale to Dong-A. But there is a possibility that Bayer may push to keep Mercilon.

Bayer AG

Bayer HealthCare Pharmaceuticals AG

Isis Pharmaceuticals Inc.

Bayer HealthCare Pharmaceuticals AG licensed exclusive development and commercialization rights to Ionis Pharmaceuticals Inc.'s ISIS-FXIRx (formerly ISIS416858), a Factor XI inhibitor in Phase II for thrombosis prevention. (May)

Isis will receive $100mm up front, a $55mm milestone payment if the program advances following a Phase II study in compromised kidney function patients, additional milestones upon the candidate's further clinical progress, plus tiered royalties in the low to high 20% range on gross sales. Bayer will take over all global clinical development as well as regulatory and commercialization tasks for ISIS-FXIRx. The antisense candidate targets Factor XI (a clotting factor produced in the liver), an essential part of the coagulation pathway. High levels of Factor XI are associated with increased risk of venous thromboembolic events (VTEs), a common problem following orthopedic surgeries. In a Phase II study in patients undergoing total knee replacement surgery, those treated with 300mg of ISIS-FXIRx experienced a seven-fold lower rate of VTEs and fewer bleeding events compared to patients given enoxaparin (the generic of Sanofi's Lovenox; a subcutaneous low-molecular-weight heparin). Although effective, other competing anticoagulants--including warfarin, oral Factor Xa inhibitors, and thrombin inhibitors--do not prevent all thromboembolic events and bleeding is still a concern, particularly with the new oral anticoagulants, for which there are no specific antidotes. Bayer's marketed anticoagulant Xarelto (rivaroxaban; an oral Factor Xa inhibitor partnered with J&J) had reduced sales in the first three months of 2015. The current deal enables Bayer to add an antisense candidate with a new mechanism of action to its robust cardiovascular pipeline. According to BioMedTracker, ISIS-FXIRx has a 33% likelihood of approval (3% above average). Future Phase II studies are planned for ISIS-FXIRx to address unmet needs, including atrial fibrillation patients who also have end-stage renal disease.

BioNTech AG

Eli Lilly & Co.

BioNTech AG teamed up with Eli Lilly & Co. to discover cancer immunotherapies. The deal will focus on new targets along with those already identified by BioNTech. (May)

The specific types of cancer involved were not disclosed, though BioNTech’s existing work (still all preclinical) is in the solid tumor space (melanoma, breast and ovarian cancers, and glioblastoma). The partners will work together to find new targets and corresponding T-cell receptors (TCR) for further development into therapeutics. Lilly paid $30mm cash up front and invested $30mm in BioNTech’s TCR and chimeric antigen receptor-focused division Cell & Gene Therapies GMBH. (Lilly’s post-investment stake was not disclosed, though BioNTech notes that the investment leaves the Big Pharma with a minority share.) BioNTech could also receive up to $300mm in development, regulatory, and sales milestones, plus tiered royalties up to double-digits.

BioNTech AG

Genmab AS

BioNTech AG and Genmab AS will work together to develop and commercialize bispecific antibodies in the area of immuno-oncology. (May)

BioNTech will provide some of its almost 200 immunomodulatory antibodies while Genmab brings its DuoBody platform, which generates and purifies bispecific human IgG1 antibodies. Genmab paid $10mm up front and could hand over $5mm in the near-term if certain of BioNTech’s assets are chosen for further development. If the partners jointly decide to bring projects forward, development costs and final product ownership will be shared equally, but if one company elects not to proceed, the other may do so under predetermined terms (including development and sales milestones, and royalties). The deal is the second for BioNTech in just over a week; it recently penned a T-cell receptor-based deal with Eli Lilly in which the biotech got $60mm up front (in cash and an equity investment) plus up to $300mm in potential milestones.

Boehringer Ingelheim GMBH

Eureka Therapeutics Inc.

Eureka Therapeutics Inc. licensed Boehringer Ingelheim GMBH an option to develop and commercialize cancer antibodies. (May)

BI pays an up-front technology access fee, research funding for each program, and, if the option is exercised, technical success milestones, option exercise fees, and other payments. Using its libraries, Eureka is responsible for identifying antibodies that recognize the cancer-associated protein WT1 inside tumors; WT1 is highly expressed in certain cancers. Eureka calls this class of antibodies the ESK series, and the antibodies are designed to mimic the binding properties of T-cell receptors. Through regular cellular processes, intracellular proteins break down and human leukocyte antigens (HLAs) carry the peptides--or fragments of those proteins--to the cell's surface where they are displayed by the major histocompatibility complex (MHC-complex). Since ESKs can target tumors with WT1 and trigger the process of bringing the WT1 peptide to the surface, the body's immune system can then take over--T-cells would recognize that peptide as being abnormal and destroy it. Under a 2014 deal, Novartis has exclusive worldwide rights to ESK antibodies from Eureka and the Memorial Sloan Kettering Cancer Center. Eureka has raised $27mm in venture financing to date.

Braeburn Pharmaceuticals SPRL

Endo International PLC

Endo Pharmaceuticals Inc.

Braeburn Pharmaceuticals SPRL received worldwide rights to Endo Pharmaceuticals Inc.'s six-month risperidone implant (EN3342), in Phase II for schizophrenia, and MedLaunch implant technology. (May)

Braeburn hopes to begin Phase III trials of the risperidone implant by the end of this year. MedLaunch (formerly called Hydron) is a subcutaneous, non-biodegradable hydrogel polymer that enables sustained-release drug delivery. Possessing flexible, tissue-like properties, the hydrogel polymer implant is more comfortable for patients, says Endo, and has good biocompatibility. Endo's marketed products Vantas and Supprelin LA are delivered via MedLaunch. Concurrent with the Endo deal, Braeburn licensed rights to another schizophrenia candidate, Oncothyreon's ATI9242. In its pipeline, Braeburn already has buprenorphine assets for opioid addiction and pain--in North America, the company holds rights to Titan Pharmaceuticals' Phase III Probuphine and Camurus' Phase II CAM2038.

Braeburn Pharmaceuticals SPRL

Oncothyreon Inc.

Braeburn Pharmaceuticals SPRL licensed development and commercialization rights to Oncothyreon Inc.'s ATI9242, an injectable oral clozapine analog for schizophrenia. (May)

The deal was done simultaneously with Braeburn's license to Endo's six-month risperidone implant and MedLaunch implant technology. Both alliances diversify Braeburn's pipeline beyond opioid addiction and pain; the company plans to resubmit for approval Probuphine (buprenorphine implant; licensed from Titan Pharmaceuticals) and has rights to Camurus' Phase II CAM2038 (buprenorphine injection). ARYx Therapeutics developed ATI9242 as an improved treatment over existing atypical antipsychotics for the negative symptoms of schizophrenia, but without the metabolic side effects, such as weight gain, and drug interactions. ARYx had advanced the compound to Phase I, but in 2011 the company suffered a setback regarding an FDA delay on its then-lead candidate naronapride. Due to lack of funding, it decided to wind down operations. A year later, Oncothyreon bought all of ARYx's assets related to ATI9242 (ARYx is eligible for 15% of sublicensing income that Oncothyreon generates). Braeburn now plans to formulate the candidate for long-acting delivery and start Phase II in 2015.

Eli Lilly & Co.

Transition Therapeutics Inc.

Transition Therapeutics Inc. continues to grow its relationship with Eli Lilly & Co., this time licensing exclusive global rights to the Big Pharma’s Phase II selective androgen receptor modulator TT701. (May)

Transition will pay $1mm up front, up to $100mm in sales milestones, and mid-single-digit royalties (Strategic Transactions assumes 4-7%). In trials, TT701 increased lean body mass and reduced fat mass, without affecting prostate specific antigen (PSA) levels. Transition will evaluate different potential indications for the compound, including androgen deficiency. The deal (as announced) appears different from previous alliances between the partners in that Lilly does not have an option to take back rights to the project following development by Transition. In 2010, the pair teamed up to develop one of Lilly’s diabetes compounds (TT401); Transition brought it through Phase I and in 2013 Lilly exercised an option to license it back. Lilly also granted Transition rights to TT601 for osteoarthritis in mid-2013, with the potential for Lilly to take that project back; the option has not been exercised in that alliance.

Enyo Pharma SAS

Poxel SA

Poxel SA licensed one-year-old Enyo Pharma SAS rights to its farnesoid X receptor (FXR; bile acid receptor) compounds for infections. (May)

Poxel retains rights for indications within its therapeutic focus including metabolic and cardiovascular conditions. Enyo is focused on creating therapies that target specific host functions for acute and chronic viral infections. The company in-licensed several patents from French National Inst. Health & Med. Res. (INSERM), which has discovered that FXR is a direct regulator of hepatitis B virus replication and has determined that the virus life cycle is dependent on the bile acids pathway. Enyo hopes to move an HBV candidate into the clinic in Q1 2016, with Phase II trials anticipated for 2017.

Fate Therapeutics Inc.

Juno Therapeutics Inc.

Fate Therapeutics Inc. granted Juno Therapeutics Inc. exclusive worldwide rights to IP surrounding its hematopoietic cell programming platform, which will be used to identify small-molecule modulators for Juno’s genetically engineered chimeric antigen receptor (CAR) and T-cell receptor (TCR) cancer immunotherapies. (May)

Fate will screen and identify the small molecules, while Juno gets development and commercialization rights to the compounds utilizing Fate’s modulators. Juno paid $5mm up front and purchased $8mm of Fate’s common shares (1mm shares at $8, a 49% premium). Fate could also get up to $50mm in target selection fees and development, regulatory, and sale milestones for each new project, plus low-single-digit royalties (Strategic Transactions assumes 1-4%). Juno will fund all activities during the four-year term of the deal, and has an option to extend the term for an additional two years. (If it exercises the option, Fate could then require Juno to buy an additional $10mm of its shares at a 120% premium to the 30-day pre-exercise market average.) Fate holds onto its IP rights for all indications outside of CAR and TCR development.

Genethon

Selecta Biosciences Inc.

Selecta Biosciences Inc. and Genethon will co-develop next-generation gene therapies. (May)

Genethon will contribute its expertise in gene therapy vectors, while Selecta adds its Synthetic Vaccine Particle (SVP) platform that's designed to optimize safety and efficacy and reduce the risk of immunogenicity. The firms seek to create gene therapeutics that can eliminate neutralizing antibodies and other undesired immune responses to the viral vector. Such candidates would, for the first time, allow for repeated systemic dosing, which would be highly beneficial in applications such as muscular dystrophies and pediatric liver metabolic diseases that use adeno-associated virus (AAV) vectors. Genethon and Selecta have identified three applications that might benefit from the collaboration and will both have rights to any resulting therapies.

Harbin Gloria Pharmaceuticals Co. Ltd.

Sucampo Pharmaceuticals Inc.

Under a 13-year agreement with the possibility for renewal, Sucampo Pharmaceuticals Inc. licensed Harbin Gloria Pharmaceuticals Co. Ltd. exclusive rights to develop and commercialize the gastrointestinal drug Amitiza (lubiprostone) in China. (May)

For the license, Harbin paid $1.5mm--$1mm within 30 days of deal signing and $500k within 30 days of IND application approval in China. The company will fund all development and commercial activities. Sucampo also receives an undisclosed payment upon achievement of a regulatory or commercial milestone. Sucampo will supply the drug at an agreed-upon price. Amitiza is a chloride channel agonist for treating chronic idiopathic constipation and opioid-induced constipation. Under previous tie-ups, Takeda sells Amitiza in the US and Canada, while Abbott commercializes in Japan.

Iroko Pharmaceuticals LLC

Endo International PLC

Litha Healthcare Group Ltd.

Iroko Pharmaceuticals LLC licensed Litha Healthcare Group Ltd. exclusive rights to commercialize Zorvolex (diclofenac) in eastern and southern African countries including Angola, Botswana, Lesotho, Madagascar, Malawi, Mauritius, Mozambique, Namibia, Republic of South Africa, Seychelles, Swaziland, Tanzania, and Zambia. (May)

Litha will obtain regulatory and pricing approvals in the licensed territories. Iroko developed Zorvolex with its SoluMatrix Fine Particle Technology, which creates NSAIDs with a reduced particle size and increased surface area, resulting in faster dissolution. The drug is approved in the US for mild-to-moderate pain and pain caused by osteoarthritis; it recently gained approval in Lebanon but isn't cleared in any other countries. Iroko has several partners for Zorvolex: Calox De Costa Rica (Latin America), EMS Sigma Farma (Brazil), Landsteiner Scientific (Mexico), Aspen Pharmacare Australia Pty. Ltd. (Australia and New Zealand), Algorithm (MENA), and PT Pratapa Nirmala (Indonesia).

Merck & Co. Inc.

PeptiDream Inc.

PeptiDream Inc. agreed to use its Peptide Discovery Platform System (PDPS) to generate macrocyclic/constrained peptides against undisclosed targets selected by Merck & Co. Inc. (May)

PeptiDream gets money up front, research funding, preclinical and clinical milestones, and potential sales royalties. Merck comes away from the deal with rights to develop and sell all peptides that PeptiDream discovers for the company, and gets an option to nonexclusively license the technology. PDPS combines Flexizyme in vitro evolved artificial ribozymes (RNA catalysts), translation, cyclization, and peptide-modifying technologies, and a peptide discovery display which together generate hundreds of macrocyclic therapeutic peptides against a single target in just weeks. Merck joins a wide of pool of other firms also benefiting from PeptiDream’s platform including Amgen, AstraZeneca, Lilly, GSK, and Novartis.

Merus Labs International Inc.

Novartis AG

Novartis Pharma AG

Merus Labs International Inc. licensed rights to manufacture and commercialize Novartis Pharma AG's marketed drugs Salagen (pilocarpine) and Estraderm MX (transdermal estradiol) in Europe and other territories. (May)

Novartis received $29.5mm up front. This marks the third time in the last few years that Novartis has licensed products to Merus. In 2012 Merus acquired the overactive bladder treatment Emselex/Enablex, and last year it bought the anticoagulant Sintrom. Now Merus brings into its portfolio Salagen and Estraderm MX, which together realized $10mm in sales in the markets covered under the deal. Salagen is indicated for xerostomia following radiation therapy and due to Sjogren's syndrome, while Estraderm MX treats menopausal symptoms. Novartis holds rights to Salagen under a 2000 alliance with MGI Pharma (now part of Eisai); J&J's Alza originally developed Estraderm and partnered it with Novartis.

NeuroVive Pharmaceutical AB

Sanofi

Through a local affiliate in the country, Sanofi licensed South Korean rights to NeuroVive Pharmaceutical AB’s CicloMulsion cyclophilin inhibitor, which is in Phase III studies to prevent reperfusion injury in cardiovascular disease. (May)

Sanofi will make an up-front and milestone payment, plus royalties, and is responsible for regulatory filings and approval, along with marketing and distribution in South Korea. NeuroVive Pharmaceutical Asia will supply the finished product to Sanofi. CicloMulsion prevents mitochondrial membrane disruption in cells damaged by injury or disease, allowing the mitochondria to heal. It also stops the intracellular activity that leads to secondary tissue damage. Under a 2012 agreement, Sichuan Pharmaceutical has rights in China.

OSE Pharma SA

Rafa Laboratories Ltd.

OSE Pharma SA granted Rafa Laboratories Ltd. exclusive rights to sell its Tedopi immunotherapy for cancer in Israel. (May)

The deal marks the first out-licensing partnership for OSE; the company was formed in 2012 and just went public on Euronext in March. Rafa pays money up front and development milestones, will submit the compound for approval in the licensed territory, and equally share Israeli profits with OSE. Tedopi (IDM2101) combines ten epitopes that were selected and optimized from five tumor-associated antigens. It will enter Phase III for HLA-A2 positive non-small cell lung cancer patients who failed previous therapies. The project originated at IDM Pharma, which was acquired by Takeda in 2009. OSE then licensed Tedopi from Takeda, and in addition to work on the compound as a monotherapy, is also planning Phase II trials in combination with another immunotherapeutic.

Sun Pharmaceutical Industries Ltd.

Tribute Pharmaceuticals Canada Inc.

Tribute Pharmaceuticals Canada Inc. acquired US rights to Sun Pharmaceutical Industries Ltd.'s cholesterol treatment Fibricor (fenofibrate) and its authorized generic. (May)

Tribute pays $5mm up front, $2mm within six months, and $3mm within 12 months. (To help fund the transaction, the company concurrently completed a private placement of 13mm common shares at a price of $0.75.) Fibricor is a lipid-regulating agent for severe hypertriglyceridemia; reducing elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, and apolipoprotein B; and increasing high-density lipoprotein cholesterol in patients with primary hypercholesterolemia or mixed dyslipidemia. Fibricor contains the lowest dose of fenofibrate available for sale in the US and is covered under four patents that expire in August 2027. Sun gained the drug in late 2012 when it gained the generics business of Takeda's URL Pharma. The current licensing agreement with Sun is Tribute's first for the US market. As a result, Tribute is setting up operations in the US (Tribute Pharmaceuticals US Inc.) and has appointed William Maichle as president. For the twelve months preceding the end of April 2015, Fibricor generated $4.7mm in US sales. Investment Banks/Advisors: VelocityHealth Securities Inc. (Sun Pharmaceutical Industries Ltd.)

Financings

Ablynx NV

Ablynx NV (developing single-domain antibody fragments called Nanobodies as therapies for various diseases) sold €100mm ($111mm) of its 3.25% senior unsecured bonds due May 2020. At the initial conversion price of €12.93, the bonds will convert into 7.7mm ordinary shares. (The market average for Ablynx shares at the time of the sale was €10.12.) (May)

Investment Banks/Advisors: Bank of America Merrill Lynch; JP Morgan Chase & Co.

Achillion Pharmaceuticals Inc.

Johnson & Johnson Development Corp. made a $225mm equity investment in Achillion Pharmaceuticals Inc., buying about 18.4mm new unregistered shares at $12.25 each (a 28% premium). Concurrently, Achillion licensed Janssen Pharmaceuticals Inc. exclusive worldwide rights to develop and commercialize hepatitis C assets including ACH3102, ACH3422, and sovaprevir. (May)

Adaptimmune Therapeutics PLC

Less than a year after closing its $104mm Series A round (the largest Series A in 2014), UK-based Adaptimmune Therapeutics PLC (T-cell therapy) netted $178mm in its US initial public offering of 11.2mm ADSs (representing 67.5mm ordinary shares) for $17. The company planned to sell 9.4mm ADSs (representing 56.2mm ordinary shares) for $15-17. (May)

Investment Banks/Advisors: Bank of America Merrill Lynch; Cowen & Co. LLC; Guggenheim Partners LLC; Leerink Partners LLC

Affimed Therapeutics AG

Affimed NV (therapeutic antibodies for cancer) netted $38.6mm through the public sale of 5.75mm common shares (including the overallotment) at $7.15. Affimed will use the money (together with existing cash on hand) to continue Phase II trials of AFM13 for Hodgkin lymphoma, as well as preclinical studies with the compound for CD+ lymphoma and in combination with checkpoint inhibitors for Hodgkin lymphoma. Proceeds will also go towards AFM11 (Phase I for NHL and ALL), and preclinical solid tumor project AFM21. (May)

Investment Banks/Advisors: BMO Financial Group; Jefferies & Co. Inc.; Leerink Partners LLC; Oppenheimer & Co. Inc.

Agenus Inc.

Agenus Inc. (developing vaccines for cancer, infectious diseases, and immune disorders) netted $65.1mm through the follow-on sale of 11mm common shares at $6.30 each. (May)

Investment Banks/Advisors: Jefferies & Co. Inc.; Oppenheimer & Co. Inc.; William Blair & Co.

Aldeyra Therapeutics Inc.

Aldeyra Therapeutics Inc. (Nasdaq: ALDX) netted $19.9mm in a follow-on public offering of 2.7mm common shares (including a partial exercise of 122,500 shares of the overallotment) at $7.50 per share. The proceeds will be used for R&D for current and future clinical trials of topical NS2; to develop systemic formulations of NS2; to develop novel aldehyde traps distinct from NS2; and to expand clinical development and regulatory infrastructure. In January of 2015 the company completed two private placements raising about $9.8mm. (May)

Investment Banks/Advisors: Canaccord Genuity Inc.; Cowen & Co. LLC; Janney Montgomery Scott Inc.; Laidlaw & Co.

aTyr Pharma Inc.

Just two months after closing a $76mm Series E round, aTyr Pharma Inc. (physiocrine-based therapies for rare diseases) went public on Nasdaq selling 6.2mm common shares (including the overallotment) at $14. The IPO, which netted $80.3mm, priced at the mid-range of aTyr's $13-15 goal. The company had planned to offer 5.4mm shares. (May)

Investment Banks/Advisors: BMO Financial Group; Citigroup Inc.; JP Morgan & Co.; William Blair & Co.

Auris Medical Holding AG

Auris Medical Holding AG (otolaryngology therapies) netted $23.6mm through the follow-on public offering of 5.3mm common shares at $4.75 each. Proceeds will support ongoing development of its Phase III AM111 for acute inner ear hearing loss. (May)

Investment Banks/Advisors: JMP Securities LLC; Leerink Partners LLC; LifeSci Capital LLC; Needham & Co. Inc.

BioInvent International AB

BioInvent International AB (therapeutic antibodies for cancer) grossed SEK77.7mm ($9.2mm) through an oversubscribed 4:9 rights issue. Shareholders subscribed to a total of 50mm new shares at SEK1.55 apiece. Proceeds will fund planned Phase I/II trials of lead projects BI205 (multiple myeloma) and BI1206 (non-Hodgkins lymphoma), and will also go toward preclinical candidates. (May)

BiondVax Pharmaceuticals Ltd.

Six months after filing, public Israeli biotech BiondVax Pharmaceuticals Ltd. (influenza vaccine development) netted $8.9mm in an oversubscribed Nasdaq IPO of 1.9mm American Depositary Shares (ADSs), or 76.4mm ordinary shares (each ADS represents 40 ordinary shares) at $5 ($0.13 per ordinary share). The company had originally offered 1.46mm ADSs. BiondVax is also offering warrants to purchase 1.91mm ADSs at $5. The five-year warrants are exercisable at $6.25 per ADS. (May)

Investment Banks/Advisors: Aegis Capital Corp.

BioTie Therapies Corp.

Finnish biotech Biotie Therapies Corp., which has traded on the Nasdaq OMX Helsinki exchange since 2002, filed for an initial public offering in the US on Nasdaq. (May)

Investment Banks/Advisors: JMP Securities LLC; RBC Capital Markets; Roth Capital Partners; Stifel Nicolaus & Co. Inc.

Catabasis Pharmaceuticals Inc.

Catabasis Pharmaceuticals Inc. (developing therapeutics based on its "Safely Metabolized And Rationally Targeted" (SMART) linker technology platform) filed for its IPO on NASDAQ. (May)

Investment Banks/Advisors: Citigroup Inc.; Cowen & Co. LLC; Oppenheimer & Co. Inc.; Wedbush PacGrow Life Sciences

Circassia Pharmaceuticals PLC

Circassia Pharmaceuticals PLC (allergy immunotherapies) raised £275mm ($426.7mm) through the private sale of 95.5mm ordinary shares at £2.88 (a 7% discount). The money will fund concurrently announced acquisitions of respiratory device firm Aerocrine AB (£139mm) and respiratory therapeutics developer Prosonix Ltd. (£70mm). (May)

Investment Banks/Advisors: JP Morgan Chase & Co.; Peel Hunt LLP

Collegium Pharmaceutical Inc.

Collegium Pharmaceutical Inc. (abuse-deterrent CNS treatments) netted $74.4mm in its IPO of 6.7mm shares (including the overallotment) for $12, the bottom end of its $12-14 price range. Existing investors (or their affiliates) may buy more than half of the IPO shares (3mm). (May)

Investment Banks/Advisors: Jefferies & Co. Inc.; Needham & Co. Inc.; Piper Jaffray & Co.; Wells Fargo Securities LLC

CoLucid Pharmaceuticals Inc.

CoLucid Pharmaceuticals Inc. (migraine) netted $51.2mm in its initial public offering of 5.5mm shares--slightly above the 5.36mm it planned--at $10, below its $13-15 range. Entities affiliated with the company's existing investors indicated they might buy $25mm in IPO shares. (May)

Investment Banks/Advisors: Ladenburg Thalmann & Co. Inc.; Piper Jaffray & Co.; Stifel Nicolaus & Co. Inc.; William Blair & Co.

Cortendo AB

Strongbridge Biopharma PLC (metabolic disease treatments) grossed $33.2mm through the sale of 25.1mm common shares at $1.32 (a 14% premium) to new backers Longwood Capital, TVM Capital (which invested $4.25mm), and Granite Point Capital, and returning shareholders RA Capital, New Enterprise Associates, Broadfin Capital, and HealthCap. (May)

Cynapsus Therapeutics Inc.

Cynapsus Therapeutics Inc., a publicly traded spec pharmaco in Canada, filed for a US initial public offering. (May)

Investment Banks/Advisors: Bank of America Merrill Lynch; Noble Financial Group; Nomura Securities International Inc.

Cytori Therapeutics Inc.

Cell therapies developer Cytori Therapeutics Inc. netted $18mm through the registered direct sale of 25.1mm units priced at $0.77. Each unit consists of one common share and one five-year warrant to buy a share at an exercise price of $1.02. Mizuho Securities (lead), Roth Capital Partners, Maxim Group, and WBB Securities were the placement agents. (May)

Investment Banks/Advisors: Maxim Group LLC; Mizuho Bank Ltd.; Roth Capital Partners; WBB Securities LLC

Dicerna Pharmaceuticals Inc.

Dicerna Pharmaceuticals Inc. (RNAi therapies for rare liver diseases and genetically defined cancers) raised net proceeds of $45.9mm through the follow-on public offering of 2.75mm common shares at $17.75 each. (May)

Investment Banks/Advisors: Cowen & Co. LLC; Jefferies & Co. Inc.; Leerink Partners LLC; Stifel Nicolaus & Co. Inc.

Galapagos NV

Belgian biotech Galapagos NV netted $224.7mm in its IPO of 5.7mm (higher than the 3.8mm planned) American Depository Shares (ADS) at $42.05 (including the over-allotment). Each ADS is equal to one ordinary share. (May)

Investment Banks/Advisors: Bryan Garnier & Co.; Cowen & Co. LLC; Credit Suisse First Boston; Morgan Stanley & Co.; Nomura Securities International Inc.

Galapagos NV

Galapagos NV (small-molecule drug candidates for multiple diseases) netted $69.5mm in a private placement of 1.8mm ordinary shares at $41.81 (€37.00), a 2% discount. European and ex-US and ex-Canadian investors participated. The company also netted $225mm in a concurrent IPO on the NASDAQ. The proceeds will be used to advance the company's cystic fibrosis, inflammatory bowel, and other early stage programs. (May)

Investment Banks/Advisors: Bryan Garnier & Co.; Cowen & Co. LLC; Credit Suisse First Boston; Morgan Stanley & Co.; Nomura Securities International Inc.

Kadmon Corp. LLC

Kadmon Gene Therapy Holdings Ltd.

Kadmon Corp. LLC spun off its gene therapy business as Kadmon Gene Therapy Holdings Ltd. (KGT), a new, independent company that will develop gene therapeutics for a variety of disorders. Kadmon will most likely take an equity stake in the new entity. (May)

Momenta Pharmaceuticals Inc.

Momenta Pharmaceuticals Inc. (develops generic versions of complex drugs) netted $148.9mm through the follow-on sale of 8.34mm common shares (including the overallotment) at $19 each. (May)

Investment Banks/Advisors: Goldman Sachs & Co.; JP Morgan & Co.; Stifel Nicolaus & Co. Inc.

Navidea Biopharmaceuticals Inc.

Navidea Biopharmaceuticals Inc. (targeted radiopharmaceuticals for cancer) received an initial $50mm of a $60mm loan from CRG. The term is six years, with the first four years interest-only (at 14%). The remaining $10mm is available at Navidea's option subject to certain conditions. The company will use the money to retire debt from Oxford Finance; support the Manocept technology (focused on CD206-targeting of macrophages for diagnostic and therapeutic applications); and fund commercialization of the Lymphoseek imaging agent for sentinel lymph node detection. (May)

NeuroVive Pharmaceutical AB

NeuroVive Pharmaceutical AB (mitochondrial medicines for cardiovascular and neurological conditions) raised SEK70mm ($8.4mm) through the sale of 1.6mm new shares at SEK42.50 (an 18% discount) to US institutional investors. Chardan Capital Markets was the placement agent. Proceeds will help fund US clinical trials and European commercialization of its myocardial infarction drug CicloMulsion (IV cyclosporine) and preclinical studies for its organ protection candidate NVP019. (May)

Investment Banks/Advisors: Chardan Capital Markets; HDR Partners AB; J. Streicher Capital LLC

Nivalis Therapeutics Inc.

Nivalis Therapeutics Inc. (cystic fibrosis therapies) filed for its initial public offering on Nasdaq. (May)

Investment Banks/Advisors: Cowen & Co. LLC; HC Wainwright & Co.; Robert W. Baird & Co. Inc.; Stifel Nicolaus & Co. Inc.

NovaBay Pharmaceuticals Inc.

Anti-infectives developer NovaBay Pharmaceuticals Inc. grossed $6.9mm through the private placement of 10.9mm units at $0.63, a 3% premium. Each unit consists of one common share and an 18-month warrant to purchase one-half of a common share at $0.78 per whole share. There's a provision for forced conversion should the common shares trade at or above $1.00 for 10 out of 20 consecutive trading days. Some of the proceeds will support the US launch of its Avenova cleanser for eyelid and eyelash infections. China Kington was the placement agent. (May)

Investment Banks/Advisors: Maxim Group LLC

PlasmaTech Biopharmaceuticals Inc.

Concurrent with the announcement that it’s buying Abeona Therapeutics for $13.65mm in stock, Abeona Therapeutics Inc. grossed $10mm through the private placement of 1.25mm common shares at $8.00 each (a 131% premium) to an institutional investor. The company also issued two-and-a-half-year warrants to buy another 625k shares exercisable at $10. HC Wainwright was the placement agent. (May)

Investment Banks/Advisors: HC Wainwright & Co.

Prima Biomed Ltd.

Prima BioMed Ltd. (cancer immunotherapeutics) raised $A15mm ($11.8mm) through the sale of equity and debt to Ridgeback Capital Management. Prima issued 72mm ordinary shares at $A0.0173 (a 50% discount) for proceeds of $A1.2mm, and also received $A13.75mm from the placement of 3% convertible notes due 2025. (The notes convert to ordinary at $A0.02.) (May)

Prometic Life Sciences Inc.

ProMetic Life Sciences Inc. (plasma-derived therapeutics) netted $Cdn54.7mm ($44.9mm) in a bought deal public offering of 22mm shares (including the overallotment) at $Cdn2.60. Proceeds will enable the company to advance clinical programs including PBI4050--its lead orphan drug-designated candidate in Phase II for idiopathic pulmonary fibrosis--and increase its manufacturing capacity for plasma-derived therapeutics. (May)

Investment Banks/Advisors: Beacon Securities Ltd.; Canaccord Genuity Inc.; Paradigm Capital Inc.; RBC Dominion Securities; TD Securities Inc.

Retrophin Inc.

Sanofi

Retrophin Inc. sold its rare pediatric disease priority review voucher (PRV) to Sanofi for $245mm. Sanofi paid $150mm up front, and will make two equal payments of $47.5mm in 2016 and 2017. (May)

Roivant Sciences Ltd.

Axovant Sciences Ltd.

Axovant Sciences Ltd. (dementia therapeutics) filed for its initial public offering. (May)

June 2015 update: Axovant set terms--17.9mm shares for $13-15.

Investment Banks/Advisors: Evercore Partners; JMP Securities LLC; Jefferies & Co. Inc.; RBC Capital Markets; Robert W. Baird & Co. Inc. (Axovant Sciences Ltd.)

TetraLogic Pharmaceuticals Corp.

TetraLogic Pharmaceuticals Corp. netted $23mm in a follow-on offering of 6.25mm shares at $4 per share. The company will use the proceeds for development of its product candidate pipeline and acquisitions. (May)

Investment Banks/Advisors: Nomura Securities International Inc.; WBB Securities LLC; William Blair & Co.

Tribute Pharmaceuticals Canada Inc.

Canadian specialty pharmaco Tribute Pharmaceuticals Canada Inc. raised $Cdn12mm ($9.9mm) through the private sale of 13mm common shares at $Cdn0.92 (a 7% discount). Dundee Securities, KES 7 Capital, and Bloom Burton were the placement agents. Proceeds will fund the concurrent in-licensing of US rights to cholesterol drug Fibricor (fenofibrate) from Sun Pharmaceutical Industries. (May)

Investment Banks/Advisors: Bloom Burton & Co.; Dundee Securities Corp.; KES 7 Capital Inc.

RESEARCH, ANALYTICAL EQUIPMENT & SUPPLIES

Mergers & Acquisitions

Danaher Corp.

Pall Corp.

Danaher Corp. acquired publicly traded Pall Corp. (global filtration and purification solutions) for $13.8bn in cash including assumed debt and net of acquired cash. The offer is for $127.20 per share in cash (a 27% announced its plans topremium). Upon closing of the transaction, Danaher will split into two publicly listed companies - a science and technology-focused company including the Pall businesses (retaining the Danaher name), and a new more industrial-focused entity. (May)

Pall generated $2.8bn in revenues ($1.5bn from its life sciences segment) in fiscal 2014 and had $1bn in cash on hand with 75% recurring revenues, and solid organic growth & margins. The company operates through two segments: life sciences, which includes customers in biopharma and food sectors, and industrials, where it serves process technologies, aerospace and microelectronics markets. The acquisition will allow Danaher to accelerate new product development and improve operational efficiency. The terms of the transaction need to be approved by the shareholders and the deal is expected to be $0.40 accretive to adjusted diluted earnings per share in 2016.