Deals Shaping The Medical Industry, December 2017

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 November 2017.

IN VITRO DIAGNOSTICS

Alliances

Clearbridge BioMedics Pte. Ltd.

Danaher Corp.

Leica Biosystems Ltd.

Leica Biosystems Ltd. and Clearbridge BioMedics Pte. Ltd. will co-promote each other’s automated systems for liquid biopsy and circulating tumor cell (CTC) analysis. (Nov.)

Included in the deal are ClearBridge’s ClearCell FX, an automated cell retrieval system that allows for the collection of intact and viable CTCs from small amounts of blood obtained in a standard blood draw. The platform, which is powered by the company’s CTChip FR1 microfluidics biochip, provides a CTC sample with high cell surface antigen expression and cell integrity, and once output, is immediately ready for downstream analysis through pathology workstations such as Leica’s BOND RX. BOND RX is a fully automated staining system for immunohistochemistry, immunofluorescence, and fluorescent in-situ hybridization assays. By marketing both products together, Leica and ClearBridge will be able to present to their drug development and diagnostics clients an integrated system for both the enrichment and immunostaining of CTCs.

Financings

Biocartis NV

Molecular diagnostics firm Biocartis NV grossed €80mm ($95.4mm) through a private placement bookbuild offering of 6.4mm new shares at €12.50 apiece (a 3% discount). Among other uses, a portion of the proceeds will support expansion of the company's Idylla fully automated molecular testing platform, menu, and applications. (Nov.)

Investment Banks/Advisors: Bank Degroof; JP Morgan Chase & Co.; KBC Securities; Kempen & Co.

Quanterix Corp.

Diagnostics firm Quanterix Corp. filed for its initial public offering on the Nasdaq. (Nov.)

Investment Banks/Advisors: BTIG LLC; Evercore Partners; JP Morgan Chase & Co.; Leerink Partners LLC

MEDICAL DEVICES

Mergers & Acquisitions

MicroPort Scientific Corp.

LivaNova PLC

MicroPort Scientific Corp. has entered into a binding letter of intent to acquire LivaNova PLC's (formerly Sorin Group) cardiac rhythm management (CRM) business for $190mm in cash. (Nov.)

The acquired CRM franchise offers high-voltage defibrillators, cardiac resynchronization therapy devices, and low-voltage pacemakers. These products provide a means for diagnosing, treating, and managing heart rhythm disorders and heart failures. For 2016 the business brought in $249mm in sales. It employs 900 people at locations in France, Italy, and the Dominican Republic. LivaNova is divesting the CRM business to focus on its cardiac surgery and neuromodulation businesses. Back in 2014, the firms created a joint venture, MicroPort Sorin CRM (Shanghai) Co. Ltd., to import, sell, and service Sorin’s CRM devices in China and to manufacture CRM products for the Chinese market. Just two months ago the FDA in China approved the JV's Rega pacemaker family, the smallest pacemakers available on the Chinese market. Investment Banks/Advisors: Barclays Bank PLC (LivaNova PLC)

Owens & Minor Inc.

Halyard Health Inc.

Owens & Minor Inc. is paying $710mm in cash to acquire Halyard Health Inc.'s surgical and infection prevention business. (Nov.)

Owens & Minor will fund the transaction with cash and debt. As a result of the transaction, it expects to obtain about $1bn in revenues and $80mm of yearly EBITDA. The acquired business offers a variety of products designed to prevent healthcare-associated infections in both the acute care and non-acute care markets. Specific products included sterilization wraps (One-Step, Quick Check, Smart-Fold), exam gloves (Purple, Lavender, Sterling), surgical drapes and gowns (Aero Blue, Aero Chrome), surgical masks and eyewear (FluidShield), and other surgical protection apparel. Owens & Minor cites the rationale for the acquisition as a means to expand its offerings to existing acute care and non-acute care customers in a wider range of markets worldwide. In addition to infection prevention and surgical solutions, Halyard also sells products for respiratory and digestive health, pain management, and IV therapy. The company spun off from Kimberly-Clark Corp. in late 2014. Investment Banks/Advisors: Bank of America Merrill Lynch; Citigroup Inc.; Lazard LLC (Owens & Minor Inc.)

Alliances

AIT Therapeutics Inc.

NitricGen Inc.

[AIT Therapeutics Inc.] entered into a letter of intent to acquire worldwide exclusive transferable rights to NitricGen Inc.'s eNOGenerator and related intellectual property. (Nov.)

NitricGen will receive $2mm in the form of an up-front payment and clinical and regulatory milestones (the majority tied to regulatory achievements). It will also get low-single-digit royalties and warrants to purchase 100k shares of AIT common stock at $6.90 each. The eNOGenerator can generate nitric oxide (NO) for delivery into the lungs at various concentrations (1-400 parts per million). Under the proposed agreement, AIT can target all conditions requiring NO at any concentration regardless of the need for intermittent or continuous dosing. At only 7 pounds, eNOGenerator is much more convenient than large high-pressure NO cylinders and can thus be used not only in the hospital but in the home setting. NitricGen had developed the product as a way to generate and deliver a safe controlled dose of gaseous nitric oxide for treating chronic wounds such as diabetic foot ulcers.

APR Applied Pharma Research SA

Mundipharma International Corp. Ltd.

Mundipharma International Corp. Ltd. licensed exclusive rights in African and the Levant Region to sell APR Applied Pharma Research SA’s Nexodyn wound cleanser. (Nov.)

Mundipharma’s rights cover over 35 African regions including Nigeria, Kenya, Egypt, Algeria, Lebanon, Jordan, Tunisia, and Morocco. Nexodyn AcidOxidizing Solution (AOS) modulates inflammatory mediators in wounds by its three key features--pure hypochlorous acid (an antimicrobial agent), low pH, and high-oxidation reduction potential. The cleanser was developed using APR’s super-oxidizing TECHLO technology, and is indicated for the debridement, irrigation, and moistening of wounds (acute and chronic), burns, ulcers, cuts, and abrasions. It received the CE Mark in 2013 and is marketed in Italy by Angelini. Mundipharma plans to launch the product in some of its territories in the coming months.

Financings

AxoGen Inc.

AxoGen Inc. (allografts and surgical tools for peripheral nerve repair) netted $15.9mm through the public offering of 805k shares (including the overallotment) at $21. Selling shareholder EW Healthcare Partners sold an additional 1.15mm shares. The company will use the proceeds for product commercialization and marketing and continued development of its pipeline. Concurrent with the closing of the offering, AxoGen announced plans to expand the indications for its surgical offerings to breast reconstruction neurotization (sensory restoration) following mastectomy and pain management in addition to the existing core areas of upper extremity trauma, nerve compression, and oral and maxillofacial procedures. (Nov.)

Investment Banks/Advisors: Cantor Fitzgerald & Co.; JMP Securities LLC; Leerink Partners LLC

Insulet Corp.

Insulet Corp. (developer of the Omnipod insulin management system) netted $340.2mm through the upsized (from $300mm) private placement of $350mm convertible senior notes due 2024. The notes will bear interest at a rate of 1.375% per annum and convert into common at a rate of 10.7315 shares per $1k principal amount, or $93.18 per share. (The company's stock averaged $61.88 at the time of the sale.) Upon conversion, the notes may be settled in cash, Insulet common shares, or a combination of the two. The firm will use the proceeds to repurchase $63.4mm principal amount of its outstanding 2.00% convertible senior notes due 2019; to potentially finance additional repurchases, redemptions, and/or the settlement of conversions of its 2.00% convertible senior notes due 2019; and invest in its manufacturing operations and international expansion. (Nov.)

Limacorporate SPA

Limacorporate SPA raised €275mm ($320mm) through the sale of senior secured notes due 2023; the notes bear interest at a rate of EURIBOR+3.75% per annum. The company also entered into a €60mm ($70mm) super senior revolving credit facility. Lima will use the funding to repay outstanding debt under an existing senior facilities agreement. (Nov.)

Neovasc Inc.

Cardiovascular device maker Neovasc Inc. netted $35.2mm through the follow-on public offering of 6.6mm Series A units priced at $1.46. Each consists of one common share, one five-year Series A warrant to purchase a share, one two-year Series B warrant to purchase a share, and 0.40 of a two-year Series C warrant to purchase a unit comprised of one common share, one Series A warrant, and one Series B warrant. The company also sold 19.1mm Series B units at $1.46. Each Series B unit consists of either one common share or one pre-funded five-year Series D warrant to purchase a share, one Series A warrant to purchase a share, one Series B warrant to purchase a share, 0.40 of a Series C warrant to purchase a unit comprised of one common share, one Series A warrant and one Series B warrant, and 1.1765 two-year Series F warrants to purchase a share. Neovasc will use the proceeds to fund the balance of the awards granted in the litigation with CardiAQ Valve related to its Tiara technology, and to help fund the ongoing Tiara transcatheter device trial. The company concurrently completed a $32.8mm private placement. (Nov.)

Investment Banks/Advisors: Canaccord Genuity Inc.

Neovasc Inc.

Neovasc Inc. (cardiovascular devices) completed a private placement of $32.8mm aggregate principal amount of senior secured convertible notes and Series E warrants to purchase one common share. The 18-month notes will be issued with an original issue price of $850 per $1,000 principal amount and carry an interest rate of 0.0% per year (increasing to 15% upon an event of default). The company concurrently netted $35.2mm through a follow-on offering and will use the proceeds from both financings to fully fund the balance of the awards granted in the litigation with CardiAQ Valve related to its Tiara technology, and to help fund the ongoing Tiara transcatheter device trial. (Nov.)

Investment Banks/Advisors: Canaccord Genuity Inc.

ReWalk Robotics Ltd.

ReWalk Robotics Ltd. (wearable robotic exoskeletons for patients with spinal cord injury) netted $7.66mm through the follow-on public sale of 7.89mm ordinary shares (including full exercise of the overallotment) at $1.05. The company will use the proceeds for sales, marketing, and reimbursement costs and for R&D expenses related to its soft suit exoskeleton technology for lower limb disabilities. (Nov.)

Investment Banks/Advisors: National Securities Corp.

Teleflex Inc.

Teleflex Inc. (products for vascular access, anesthesia, and respiratory, cardiac, general surgical, and urology procedures) netted $493.7mm through the sale of $500mm 10-year senior notes (mature on November 15, 2027). The notes bear interest at a rate of 4.625%, payable semi-annually each May 15 and November 15. The company plans to use the offering proceeds to repay existing debt under its revolver. (Nov.)

Investment Banks/Advisors: Bank of America Merrill Lynch; Citigroup Inc.; DNB ASA; Guggenheim Partners LLC; HSBC; JP Morgan & Co.; PNC Financial Services Group Inc.; SMBC Nikko Securities Inc.; US Bancorp Piper Jaffray; Wells Fargo Securities LLC

PHARMACEUTICALS

Mergers & Acquisitions

Astellas Pharma Inc.

Mitobridge Inc.

Astellas Pharma Inc. has exercised its option to acquire Mitobridge Inc. (formerly Mitokyne). (Nov.)

In October 2013, the firms penned a potential $730mm deal involving the discovery, development, and commercialization of drugs that improve mitochondrial function. Mitobridge (then known as Mitokyne) was in charge of R&D and delivery of IND candidates to Astellas, which was responsible for clinical trials and commercialization. In addition to getting rights to resulting drugs, Astellas had the exclusive option to acquire the company outright. Concurrent with that agreement, Astellas also participated in the firm's $45mm Series A in which MPM Capital and Longwood Founders Fund each participated. Terms of the acquisition call for Astellas to pay $225mm up front and potentially another $225mm based on clinical development of various programs. However, the actual up-front payment will be $165.5mm once Astellas' existing stake in Mitobridge is factored in. Post-acquisition, Mitobridge will become a wholly owned Astellas subsidiary. The most advanced program coming out of the 2013 alliance was MA0211, a PPAR-delta modulator currently in Phase I for Duchenne muscular dystrophy. The candidate is designed to reverse the mitochondrial defects that cause DMD to progress. Mitobridge's pipeline also has preclinical programs for liver, kidney, neurodegenerative, muscle, and ophthalmic diseases.

Mallinckrodt PLC

Ocera Therapeutics Inc.

Mallinckrodt PLC is acquiring US-based Ocera Therapeutics Inc., a publicly-traded firm developing a treatment for hepatic encephalopathy (HE). (Nov.)

Ocera’s sole candidate is OCR002, an ammonia scavenger in Phase II trials for HE, a neuropsychiatric syndrome associated with hyperammonemia (a complication of chronic or acute liver disease). The candidate works by eliminating excess ammonia in the bloodstream and excreting it through the kidneys. It has orphan drug designation in the US and Europe, as well as fast-track designation in the US; Mallinckrodt plans to initiate Phase III trials of both an IV and oral formulation, with targeted launch dates for both forms by 2022 and 2024, respectively. It will pay $1.52 per share (a 46% premium; roughly $42mm) to acquire all of Ocera’s outstanding stock, and will also issue Ocera shareholders one Contingent Value Right (CVR) to receive payments in cash of up to $2.58 per share based on certain milestones. (In aggregate, CVRs could result in payments of $10mm upon enrollment of the first patient in a Phase III oral trial with OCR002; $15 when the first patient is enrolled for the Phase III intravenous trial; and $50mm when cumulative product sales first exceed $500mm.) The acquisition builds out Mallinckrodt’s hepatic and renal disease pipeline, and is complementary to the company’s Phase III hepatorenal syndrome asset terlipressin.

Melinta Therapeutics Inc.

The Medicines Co.

The Medicines Co. is selling its infectious disease business to Melinta Therapeutics Inc. for $270mm in up-front and earn-out payments, plus royalties ranging from 5-25% on global sales of three antibiotics. (Nov.)

The acquisition includes global rights for three marketed drugs--recently launched Vabomere (meropenem/vaborbactam) for urinary and respiratory tract infections, Orbactiv (oritavancin) for skin and skin-structure infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus, and Minocin (minocycline) for infections due to susceptible strains of several gram-positive and gram-negative pathogens--as well as the business supporting those products. The deal positions Melinta as a pure-play antibiotics firm with TMC's antibiotics joining its pipeline containing Baxdela (delafloxacinfor), which is approved for acute bacterial skin and skin structure infections, but also in various stages of clinical development for other infections. Specific terms of the agreement are Melinta paying out $165mm in cash and $55mm of its common shares up front. In addition, it will shell out $25mm in cash one-year after the deal closes and another $25mm in cash on the 18-month anniversary of the closing. Royalties are as follows: 5% for US net sales of Vabomere above $50mm and at or below $100mm, 7.5% for sales above $100mm and at or below $200mm, 15% for sales over $200mm and at or below $500mm, and 25% on sales exceeding $500mm; 5% for combined US sales of Orbactiv and Minocin IV at or below $100mm and 15% on sales over $100mm; for combined sales of Vabomere, Orbactiv, and Minocin outside the US, the royalty rate is 15%. TMC royalty rights can be transferred to a third party, including a royalty monetization transaction. The divestiture allows TMC to focus exclusively on its Phase III cholesterol drug candidate inclisiran, which the firm expects will compete with the likes of Amgen's Repatha (evolocumab; generated 2016 sales of $101mm) and Regeneron's Praluent (alirocumab; US sales of $61.5mm last year). According to BioMedTracker inclisiran has a 56% likelihood of approval (9% above average). TMC announced its strategic plans to move towards concentrating on the drug back in late 2015. Soon thereafter the firm ponied up $175mm in cash up front and a potential $235mm in milestones for three of Mallinckrodt PLC's hemostasis brands. In May 2016 TMC sold Chiesi Farmaceutici SPA three cardiovascular assets for $260mm up front and up to $480mm in sales milestone payments. The current deal with Melinta comes just over four months after Melinta merged with Cempra to create an industry leading anti-infectives company. In conjunction with the closing of the TMC acquisition, Melinta entered into an agreement with Deerfield Management in which the private equity firm will initially provide $190mm in debt (six-year term with interest rate of 11.75%) and equity financing (giving Deerfield a 10% stake). An additional $50mm in debt is available to Melinta within 24 months of the acquisition close upon the achievement of $75mm in annualized sales measured on the basis of its most recent six-month business period. Melinta will use the financing to fund the up-front payment for the TMC acquisition and to retire $40mm in debt. Deerfield will also earn a low-single-digit royalty on sales of Vabomere when the drug exceeds $75mm in sales and ending when sales exceed $500mm. In addition to the funding from Deerfield, certain Melinta investors are committed to make a $30mm equity investment at closing. Concurrent with the agreement, Deerfield Management has provided TMC with a $100mm loan that bears an interest of 5% per annum and, if drawn upon, will mature on the earlier of either the closing of the Melinta transaction or one year. Investment Banks/Advisors: Citigroup Inc. (The Medicines Co.)

OncoResponse Inc.

Paganini Biopharma Inc.

Two-year old OncoResponse Inc. acquired fellow privately owned cancer biotech Paganini Biopharma Inc. for an undisclosed sum. (Nov.)

Paganini was formed based on technology licensed from UCLA. The company brings to OncoResponse an anti-epithelial membrane protein 2 (EMP2) fully human mAb which OncoResponse has coded ONCR201. EMP2 is over-expressed in endometrial and ovarian cancers, as well as triple-negative breast cancer. The candidate is slated to begin clinical trials in 2019, with potential as both a monotherapy and in combination with immunotherapies. OncoResponse adds ONCR201 to a pipeline that already includes projects for melanoma, non-small cell lung cancer, prostate and gastric cancers, and chronic myeloid leukemia. The company was spun out of MD Anderson Cancer Center and Theraclone in 2015 and raised $22.5mm through a Series A round that closed last year. Paganini reportedly approached one of OncoResponse’s investors for funding, at which point the investor suggested the possibility of an acquisition.

Shanghai Pharmaceuticals Holding Co. Ltd.

Cardinal Health Inc.

Cardinal Health China

Shanghai Pharmaceuticals Holding Co. Ltd. agreed to buy Cardinal Health's Cardinal Health China (CHC) distribution business for $1.2bn. (Nov.)

The acquisition is limited to Cardinal's Chinese pharmaceutical and medical products distribution assets and does not include Cordis (acquired in 2015); its patient monitoring and recovery business acquired from Medtronic earlier this year; its medical sourcing division; or any other Cardinal subsidiaries in China. Ranked as China's number eight distributor, CHC's offerings include pharmaceuticals, medical devices, surgical supplies, specialty pharmaceuticals, vaccines, diagnostics, and consumer health products. It boasts a network covering 322 cities, offers direct distribution to more than 7k healthcare institutions (including hospitals, outpatient surgery centers, retail pharmacies, personal care stores, and e-commerce) across 11 major Chinese cities, has 28 pharmacies in 20 cities, and provides importation and logistics services. Cardinal announced in July 2017 that it was seeking alternatives for its CHC division to effectively sustain its growth. Shanghai Pharmaceuticals, with its existing distribution subsidiaries and pharmaceutical manufacturing units across China, believes it can effectively support CHC; the addition of CHC's distribution capabilities (with 15 centers across China) will enhance and grow Shanghai's existing infrastructure and enable it to explore additional opportunities in both China and the US. Investment Banks/Advisors: Lazard LLC (Cardinal Health Inc.)

Alliances

Alkermes PLC

Biogen Inc.

Alkermes PLC licensed Biogen Inc. exclusive worldwide rights (including the right to sublicense) to develop, manufacture, and commercialize ALKS8700, which is a Phase III small-molecule prodrug of monomethyl fumarate for treating relapsing forms of multiple sclerosis. The rights also extend to other products that incorporate Alkermes' intellectual property. (Nov.)

In return for the license, Alkermes receives $28mm up front, a $50mm payment if Biogen opts to continue in the collaboration following Phase III safety results, and a $150mm milestone upon FDA approval of ALKS8700 on or before December 31, 2021. (The NDA is expected to be submitted in 2018.) Alkermes also receives a royalty in the mid teens on global sales of ALKS8700 (possibly subject to minimum annual payments for the first five years after FDA approval), and tiered royalties ranging from high-single-digits to low-double-digits of products other than ALKS8700 (Strategic Transactions assumes 7-29%). Alkermes will develop ALKS8700 until FDA approval, after which Biogen takes over development and associated costs. Biogen will pay half of the development costs incurred by the Alkermes in 2017. Alkermes retains the right to manufacture clinical and commercial supplies of any products, subject to Biogen’s right to manufacture (or have manufactured) commercial supplies. Biogen holds expertise in the area of MS as evidenced by the success of its Tecfidera (dimethyl fumarate). Alkermes plans to seek approval of ALKS8700 under the 505(b)(2) regulatory pathway referencing Tecfidera, and the registration package will include pharmacokinetic bridging studies that establish bioequivalence of the compound to Tecfidera as well as from a two-year Phase III safety trial. For 2016, the drug generated nearly $4bn in worldwide sales. ALKS8700 is designed to rapidly and efficiently convert to monomethyl fumarate in the body and to offer a better differentiated gastrointestinal tolerability compared to Tecfidera. In addition, ALKS8700 is patent protected until 2033. According to Biomedtracker ALKS8700 has a 57% likelihood of approval, which is 5% above average).

AstraZeneca PLC

MedImmune LLC

PhaseBio Pharmaceuticals Inc.

MedImmune LLC granted PhaseBio Pharmaceuticals Inc. exclusive global rights to MEDI2452 (renamed PB2452), which is entering Phase I trials as a reversal agent for the anticoagulant ticagrelor (marketed as Brilinta). Financial terms were not disclosed. (Nov.)

Ticagrelor inhibits the P2Y12 receptor, a key protein responsible for platelet aggregation, and is prescribed as an anticoagulant. It is unique from other P2Y12 inhibitors in that ticagrelor can reversibly bind to the receptor, making it the only oral antiplatelet drug that can be reversed if needed (in the case of severe bleeding or the need for immediate surgery). MEDI2452, an intravenous Fab antibody fragment, demonstrated in preclinical studies the ability to attach to ticagrelor, reverse platelet aggregation caused by the drug, and thus normalize bleeding. PhaseBio plans to commence Phase I studies during the first half of 2018. The candidate diversifies the company’s pipeline beyond cardiopulmonary therapeutics; it currently has projects in various stages of development for conditions including pulmonary arterial hypertension, DMD-related cardiomyopathy, cystic fibrosis, and heart failure.

AstraZeneca PLC

G1 Therapeutics Inc.

G1 Therapeutics Inc. will study its investigational CDK inhibitor G1T38 in combination with AstraZeneca PLC’s EGFR inhibitor Tagrisso (osimertinib) under a recently signed clinical trial collaboration. (Nov.)

G1T38 is an oral CDK4/6 inhibitor that G1 is studying in Phase II ER+, HER2- breast cancer trials and in preclinical studies for non-small cell lung cancer. The candidate has strong potential when used in combination with other compounds, including growth signaling inhibitors, leading the company to pursue a combo regimen with AZ’s Tagrisso, which is already marketed for NSCLC and is in earlier trials for liver cancer. G1 will sponsor and conduct a Phase I/IIb trial of G1T38/Tagrisso in patients with the EGFR T790M mutation whose disease has progressed while on first-line EGFR inhibitors. The study is expected to begin in early 2018.

AstraZeneca PLC

Moderna Therapeutics LLC

Continuing a successful relationship that began four years ago, Moderna Therapeutics LLC and AstraZeneca PLC penned a new agreement in the cardiovascular space, this time to develop and sell a messenger RNA (mRNA) therapeutic encoding for the relaxin protein. (Nov.)

Under terms of the new deal, Moderna will fund and carry out preclinical studies of AZD7970, an mRNA therapy that promotes production and expression of relaxin, a secreted protein that is beneficial to cells impacted by heart failure and could potentially lead to heart tissue regrowth, renal function improvement, and hepatic portal pressure relief. AZD7970 incorporates Moderna’s propriety N2GL formulation, which allows for systemic repeated dosing. This aspect makes the candidate an attractive alternative to other relaxin-based projects, including Novartis’s serelaxin (RLX030), which failed in Phase III trials after it didn’t show any positive long-term effects. (With a half-life of around two hours, Novartis infused the drug continuously over a 48-hour period, but it did not provide desired results. Moderna’s mRNA formulation keeps molecules stable in the system over a longer period of time, which helps cells produce the drug longer.) AZ is responsible for early clinical trials, after which point the partners will work together on and fund late-stage development. US commercialization rights will be split under a 50/50 profit sharing agreement, while ex-US marketing will be led by AZ (with Moderna receiving tiered royalties up to double-digits on ex-US sales). In 2013, the partners teamed up to develop AZD6801, a localized mRNA therapy that encodes for VEGF-A and is entering Phase IIa trials in heart failure patients who need cardiac bypass grafting surgery. Moderna notes that AstraZeneca is one of the company’s largest shareholders.

Bayer AG

Loxo Oncology Inc.

Loxo Oncology Inc. licensed Bayer AG co-exclusive worldwide rights to its Phase II TRK (tropomyosin receptor tyrosine kinase) fusion inhibitors larotrectinib and LOXO195. (Nov.)

Bayer pays $400mm up front and a total of $650mm in regulatory and first commercial sales milestones related to events in undisclosed major markets--$450mm for larotrectinib and $200mm for LOXO195. In addition, Bayer is responsible for a $25mm milestone tied to US net sales, and outside the US, the company will pay $475mm in sales milestones and tiered, double-digit royalties. The partners will co-promote the therapies in the US--with Loxo targeting laboratory specialists and pathologists, and Bayer focusing on oncologists--and will equally split commercial costs and profits. Loxo has the option to pull out of the co-promote agreement; in that case, it would receive a low 30% royalty range on US sales instead of the profit split. Loxo will also lead US development and regulatory activities. Elsewhere in the world, Loxo is in charge of development, but Bayer will lead regulatory and commercialization efforts. The companies will share ex-US development expenses equally. Bayer will book global revenues. The transaction additionally carries a standstill provision that prevents Bayer from taking an equity stake of 5% or more in Loxo voting securities. Larotrectinib and LOXO195 are part of a group of compounds that Loxo was founded around in 2013. The company got the programs from Array BioPharma. Their deal also involves 12 other targets beyond TRK. Both larotrectinib and LOXO195 are in multiple Phase II studies covering a broad range of cancers including non-small cell lung, thyroid, and breast cancers. LOXO195 is designed for patients who respond to larotrectinib, but develop resistance. Larotrectinib is one of a few targeted cancer therapies that are involved in a basket trial, in which patients are recruited and selected based on a molecular signature, rather than the tissue type of the tumor. The FDA recently approved the first such tissue-agnostic product when it cleared Merck & Co.'s Keytruda for unresectable or metastatic solid tumors identified with the MSI-high or mismatch repair deficient biomarkers. Under a 2017 collaboration with Loxo, Ventana Medical Systems is developing a companion diagnostic for larotrectinib. Loxo expects to file an NDA for the candidate in Q4 2017 or Q1 2018. Bayer has a substantial portfolio of targeted cancer therapies including Stivarga, Nexavar, and the recently approved Aliqopa.

Bayer AG

PeptiDream Inc.

In a discovery and license collaboration valued up to $1.1bn, Japanese pharma PeptiDream Inc. will use its Peptide Discovery Platform System (PDPS) technology to identify macrocyclic/constrained peptides against multiple targets chosen by Bayer AG. (Nov.)

The deal value is composed of an undisclosed up-front payment; research funding; preclinical, clinical and commercialization milestones of up to $1.11bn (¥124.5bn); and undisclosed royalties on sales. Bayer will hold the rights to develop and commercialize any compounds identified in the collaboration. The agreement also includes an exercisable option which would give Bayer an extension of the license to include peptide-drug conjugate, diagnostic, bio-imaging, and agricultural applications. PDPS is a next-generation hit-finding platform which combines the following three main technologies: Flexizyme/PDTS (ribosome and transcription-translation system for ribosomal peptide synthesis), Cyclization/Modification Technologies (diverse libraries of constrained or cyclized peptides), and PD Display (library selection to allow for hit candidate identification). PeptiDream is currently involved in discovery collaborations with 17 large pharma companies and has transferred its PDPS platform for broad use to BMS, Novartis, Lilly, Genentech, and Shionogi. Also very active is Bayer, who just last week inked a major license agreement with Loxo Oncology worth up to $1.55bn for solid tumor candidates larotrectinib and LOXO195.

Boehringer Ingelheim GMBH

Dicerna Pharmaceuticals Inc.

Boehringer Ingelheim GMBH entered into a license agreement with Dicerna Pharmaceuticals Inc. in which the companies will use Dicerna's GalXC RNAi technology to develop therapeutics that target a specific disease-linked gene in the hepatocytes for chronic liver disease. (Nov.)

BI must pay Dicerna up to $201mm, consisting of $10mm up front and success-based development and commercialization milestones of up to $191mm, plus potential staggered royalties tiered from high single-digits to low double-digits (Strategic Transactions assumes 7% to 29%) on worldwide net sales. While the partnership will initially focus on developing products against one specific target gene for treating nonalcoholic steatohepatitis (NASH), the companies have an option to later develop further candidates that target a second gene. Dicerna will be responsible for discovery and initial profiling (including preclinical studies), while BI will evaluate and select the candidates for further development. If BI chooses one or more candidates to license it will then be responsible for further preclinical work, along with all clinical development, manufacturing, and commercialization activities. The GalXC technology uses RNAi to inhibit expression of disease-causing genes by destroying the messenger RNA of those genes. This approach enables addressing previously inaccessible drug targets to protect and restore liver functionality in NASH patients. Additionally, GalXC offers highly specific binding to gene target, long duration of action, and an infrequent subcutaneous dosing regimen. As the technology can be applied across multiple therapy areas, BI may be able to utilize it with its cardiometabolic pipeline.

Boehringer Ingelheim GMBH

HitGen Ltd.

HitGen Ltd. entered into a drug discovery collaboration in which it will identify novel small molecules for targets of interest to Boehringer Ingelheim GMBH. (Nov.)

While specific financial details of the agreement were not disclosed, BI agreed to make up-front payments and milestones to HitGen resulting from any licensing activity. HitGen will use its technology platform based on DNA-encoded library design and synthesis and screening to find the leads for BI. The company's DNA-encoded chemical libraries contain more than 90 billion novel, diverse, drug-like small-molecule and macrocycle compounds.

Boehringer Ingelheim GMBH

iPharma (H.K.) Ltd.

IPharma (H.K.) Ltd. licensed exclusive worldwide rights to Boehringer Ingelheim GMBH's BI853520. (Nov.)

BI853520, a focal adhesion kinase inhibitor (FAKi), has completed Phase I trials for multiple solid tumors, including advanced pancreatic adenocarcinoma, platinum-resistant ovarian cancer, esophageal cancer, and soft tissue sarcoma. FAKs control a variety of cellular functions important for tumorigenesis and its inhibition has been shown to be a factor in halting tumor growth and metastasis via cancer cell- and immune-mediated effects. IPharma is expected to initiate Phase I/II studies in 2018 for BI853520 in combination with immune checkpoint inhibitors. In exchange for the rights, iPharma is required to pay BI an undisclosed up-front payment along with future milestones and royalties. IPharma was formed as a 2016 joint venture between Chinese investor I-Bridge Capital and Israeli biotech BioLineRx Ltd. with a focus on treating unmet medical needs in China. The JV team has already brought more than 10 novel candidates into trials in the APAC region.

Boehringer Ingelheim GMBH

MiNA Therapeutics Ltd.

Sosei Group Corp.'s strategic minority investment company MiNA Therapeutics Ltd. agreed to partner with Boehringer Ingelheim GMBH to develop treatments for fibrotic liver diseases, including NASH. (Nov.)

The companies will seek to identify targets that restore the metabolic functionality of epatocytes and prevent fibrotic tissue formation in patients with NASH. The deal represents MiNA's first major collaboration since Sosei made a $45.2mm equity investment (for a 25.6% stake and the option to acquire it outright) in May 2017, and leverages the company's expertise in small activating RNA therapeutics. Per the terms of the agreement, MiNA will receive an up-front payment and research funding from BI as well as potential research, development, and regulatory milestone payments of up to €307mm ($356.1mm), along with double-digit royalties on sales. Just the other day BI inked a similar deal with Dicerna Pharmaceuticals in which the companies will use Dicerna's GalXC RNAi technology to develop therapeutic compounds that target a specific disease-linked gene in the hepatocytes for chronic liver disease. Investment Banks/Advisors: Ferghana Partners (MiNA Therapeutics Ltd.)

Cue Biopharma Inc.

Merck & Co. Inc.

Cue Biopharma Inc. and Merck & Co. Inc. entered a multi-year partnership to develop engineered biologics for autoimmune diseases. (Nov.)

The partners will use Cue’s CUE Biologics platform (Conditional and Unique Engagement of T cells) to develop candidates that are engineered to selectively modulate T-cell subsets relevant to undisclosed autoimmune diseases and dampen disease-causing T-cell response. Merck made an up-front payment and will hand over up to $374mm in development, regulatory, and sales milestones, plus tiered royalties. Compounds designed using the CUE Biologics technology mimic antigen presenting cells to deliver immune signals to diseases cells. In addition to immune conditions, the platform is also applied to cancer cells in the opposite manner (instead of ablating the T-cell response, CUE Biologics for cancer selectively activate such responses). The technology is based on IP that Cue licensed from the Albert Einstein College of Medicine. The company was formed in 2015, and is currently pursuing an initial public offering following two rounds of venture funding (totaling $26.4mm).

Homology Medicines Inc.

Novartis AG

Novartis Institutes for BioMedical Research Inc.

Novartis AG licensed exclusive worldwide rights to Homology Medicines Inc.'s AMEnDR (AAV-Mediated Editing by Direct Homologous Recombination) gene editing technology platform to develop therapeutics for a blood disease and select ophthalmic targets. (Nov.)

In exchange for its global license, Novartis--a participant in Homology's August 2017 $83.5mm Series B round--provided an up-front payment and will make another equity investment in the company. Homology will also receive research funding to advance development programs, milestone payments, and sales royalties. Homology retains US commercialization rights and shares US profits with Novartis for in vivo applications within hemoglobinopathy, one therapeutic focus of the 2015 start-up (which is also pursuing a pipeline of gene therapies in metabolism, CNS and lysosomal storage disorders, and other rare genetic diseases). The AMEnDR platform corrects gene defects using a natural DNA repair mechanism in which homology sequences are designed and engineered to precisely target a specific region of the genome and then delivered using adeno-associated virus (AAV) vectors. The company has demonstrated in preclinical studies the ability of its AAV vectors to cross the blood brain barrier and provide biodistribution to multiple tissue types, including liver, muscle (skeletal and cardiac), ocular, and CNS. The AMEnDR technology, which can be used in gene correction, insertion, or knockout, eliminates the off-target effects potentially seen in nuclease-based gene editing approaches. CRISPR, one such technique the Novartis Institutes for BioMedical Research is also exploring, can easily disrupt a gene sequence (by insertion or deletion), but proves more challenging in fixing a gene error. Novartis will exploit Homology's technology to pursue a single AAV candidate for direct injection into the bloodstream to fix a defective gene causing a blood disease; therapies delivered locally to the eye in ophthalmic diseases; and NIBR-nominated research projects in potentially other therapeutic areas.

I-MAB Biopharma

MorphoSys AG

MorphoSys AG granted I-MAB Biopharma exclusive rights in China, Taiwan, Hong Kong, and Macao to MOR202, a CD38 antagonist in Phase II trials for relapsed/refractory multiple myeloma. (Nov.)

I-MAB will pay $20mm up front, up to $100mm in development and sales milestones, and tiered double-digit royalties. The HuCAL antibody was part of a 2013 deal with Celgene through which MorphoSys had granted Celgene exclusive global development and commercialization rights in return for close to $820mm ($154mm in cash and equity up front and the remainder in milestones), but the partners mutually terminated the deal in 2015 and all rights were returned. I-MAB now plans to initiate trials in China within the next year. The company was formed earlier this year as a result of the merger between Tasgen Bio-Tech and Third Venture Biopharma. The combined entity’s pipeline holds a number of candidates in various stages of development for immuno-oncology and autoimmune diseases.

Johnson & Johnson

Janssen Biotech Inc.

Zymeworks Inc.

Zymeworks Inc. licensed Janssen Biotech Inc. global rights to use its Azymetric and EFECT (Effector Function Enhancement and Control Technology) platforms in the research, development, and commercialization of up to six bispecific antibodies against Janssen targets. (Nov.)

In exchange for the rights, Janssen will pay Zymeworks $50mm up front, up to $282mm in development milestones, up to $1.12bn in sales milestones, and tiered royalties. Janssen has an option to develop two additional bispecific antibodies and would pay an option fee to Zymeworks. With a potential value of $1.5bn, the deal is Zymeworks' largest to date. The Azymetric technology enables monospecific antibody candidates to provide dual targeting of receptors and ligands, with immunoglobulin-1-like biophysical and functional properties and manufacturability. The EFECT platform enables up or down regulation of antibody-mediated immune cell interactions. Zymeworks has been using the Azymetric technology in the development of its lead asset ZW25, a HER2-targeting bispecific currently in Phase I for breast, gastric, and ovarian cancers. The company plans to use most of the proceeds from the Janssen collaboration to fund ongoing trials of ZW25, and to move preclinical programs into human trials. Janssen is Zymeworks' sixth major partner followed by previous agreements with Daiichi Sankyo (2016), GSK (2016 and 2015), Celgene (2015), Lilly (2014), and Merck (2011).

Kwangdong Pharmaceutical Co. Ltd.

Palatin Technologies Inc.

Korean pharmaceutical firm Kwangdong Pharmaceutical Co. Ltd. gained exclusive Korean development and commercialization rights to Palatin Technologies Inc.'s Rekynda (bremelanotide) for female sexual dysfunction (FSD). (Nov.)

Kwangdong will handle all clinical development and regulatory activities required for commercialization within its territory, paying Palatin $500k up front, $3mm upon bremelanotide's first commercial sale in Korea, up to $37.5mm in sales milestones, and mid-single-digit to low double-digit royalties (Strategic Transactions assumes 4-29%). Administered subcutaneously using a single-use autoinjector pen, bremelanotide (a synthetic peptide analog) is believed to activate melanocortin, a pathway known to be involved in sexual desire and response. In August 2016 Rekynda completed Phase III trials for the on-demand treatment of hypoactive sexual desire disorder (HSDD; the single-largest specific FSD diagnosis) in premenopausal women, meeting both efficacy endpoints. An NDA filing is expected in Q1 2018. Under separate agreements earlier this year, Palatin granted exclusive development and commercialization licenses for bremelanotide to both AMAG Pharmaceuticals (in North America) and Fosun Pharma (in China, Taiwan, Hong Kong, and Macau). The current deal furthers Palatin's global market growth for the candidate and enables Kwangdong to expand its existing portfolio of OTC and ethical pharmaceuticals (in areas including cancer, CNS, metabolic, respiratory, and urinary) into women's health.

Merck KGAA

Orexigen Therapeutics Inc.

Orexigen Therapeutics Inc. penned a deal with Merck KGAA for marketing and distribution of Orexigen's obesity drug Contrave (burpropion/naltrexone) in Latin America (including Brazil, Mexico, Argentina, Chile, Bolivia, Paraguay, Uruguay, Colombia, Ecuador, Peru, Venezuela, Honduras, Guatemala, Dominican Republic, Nicaragua, Panama, Costa Rica, Belize, and El Salvador). (Nov.)

Orexigen chose Merck because of its strong presence in Latin America and its experience in the field of obesity and related complications. Merck will make an up-front payment plus regulatory and sales milestones, and is responsible for all regulatory and commercialization activities. Orexigen will supply Contrave to Merck. The drug is marketed in 67 countries globally (also under the name Mysimba) through partners including Valeant, Rovi, Biologix FZCo., Bruno, Navamedic, and Cheplapharm. Orexigen is currently in discussions with additional companies for marketing of the therapy in the EU and other ex-US countries.

NanoCarrier Co. Ltd.

Vascular Biogenics Ltd.

Vascular Biogenics Ltd. (VBL) licensed NanoCarrier Co. Ltd. exclusive rights to develop and commercialize its lead cancer compound VB111 (ofranergene obadenovec) in Japan for all indications. (Nov.)

For the license, NanoCarrier will pay $15mm up front, more than $100mm in potential development and sales milestones, and tiered royalties in the high teens. NanoCarrier will handle all development, regulatory activities, and commercialization of VB111 in Japan and VBL will supply the product. VB111 is a gene therapy in various stages of development for a number of oncology indications--Phase III for recurrent glioblastoma; Phase II for thyroid, ovarian, peritoneal, fallopian tube, and endometrial cancers and sarcoma; Phase I for non-small cell lung, neuroendocrine, and renal cancers; and preclinical studies for melanoma. The companies plan to explore future oncology partnerships with each other.

Neurimmune Holdings AG

Ono Pharmaceutical Co. Ltd.

Swiss biotech Neurimmune Holdings AG is teaming up with Japanese company Ono Pharmaceutical Co. Ltd. to develop human-derived monoclonal antibodies to treat neurodegenerative diseases. (Nov.)

In exchange for exclusive worldwide development and marketing rights to resulting product candidates, Ono makes an up-front payment and will be responsible for research fees, R&D success milestones, and sales royalties. Using its Reverse Translational Medicine (RTM) platform, Neurimmune plans to discover, generate, and validate mAbs against a target for neurodegenerative diseases, which Ono will develop and market. The RTM molecular engineering technology, using high-throughput analyses of human immune responses to disease-related proteins in selected populations, identifies antibodies with superior biophysical, pharmacological, and safety properties, preserving those favorable qualities to create highly optimized drugs. Neurimmune's development efforts are already heavily concentrated in CNS, including lead Alzheimer's disease candidate aducanumab (now in Phase Ib), discovered using RTM under a 2007 collaboration with Biogen (which later went on to acquire three of Neurimmune's RTM-derived neurology programs in Parkinson's disease, AD, and dementia in 2010). For Ono, with its mostly cancer-focused pipeline, the current neurodegenerative disease deal is an opportunity to further expand into this therapeutic area. It has a 2013 partnership with Bial--from which it licensed Japanese rights to ONO2370 (opicapone), a COMT inhibitor now in Phase II in Japan for PD (and approved in the EU as Ogentys)--as well as a 2005 partnership with Novartis for Japanese rights to the Exelon rivastigmine transdermal patch for AD (approved in Japan in 2011). Ono was also developing internally ONO2160 (a carbidopa/levodopa prodrug) for PD, but discontinued it earlier this year after Phase I trials failed to show efficacy.

Nihon Trim Co. Ltd.

Human Life CORD Japan Inc.

Tissue Genesis LLC

Human Life CORD Japan Inc. licensed exclusive commercialization rights in China and Japan to certain Tissue Genesis LLC stem cell processing products for commercial applications and medical research. (Nov.)

Under the deal's 10-year term, HLC will exclusively market in Chinese and Japanese clinics, research institutions, and hospitals TG's Icellator automated stem cell isolation system. In a procedure that takes about an hour, the Icellator collects a patient's own cells from excess adipose (fatty) tissues to produce stromal vascular fraction (SVF) cells, which are then isolated, purified, and processed. The SVFs can later be re-injected back into other parts of the body as regenerative stem cell therapies. HLC and TG will together conduct activities related to the system's regulatory approval in Asia, with a first indication in breast reconstruction, for which a clinical trial is in progress in Japan at the at Kansai Medical University. The Icellator is already approved in multiple countries, including Korea, the Ukraine, and the Bahamas. US clinical trials are in progress for critical and lower-limb ischemia, amputation site pain, and erectile dysfunction. The company also believes it has potential in additional tissue regeneration indications, including osteoarthritis, diabetic leg pain, and cranio-fascial trauma. TG also offers other cell culture and tissue processing products such as Icellator cartridges and the Adipase blend of functionally screened, characterized, and optimized enzymes used to maximize cell isolation yields from adipose tissues. HLC was established earlier this year as a private regenerative medicines division of the diversified public Japanese conglomerate Nihon Trim Co. Ltd. (uses electrolysis technology in applications related to purified drinking water).

OncoQuest Inc.

Tesaro Inc.

Tesaro Inc. and OncoQuest Inc. partnered to evaluate the combination of Tesaro’s Zejula (niraparib) with OncoQuest’s oregovomab for recurrent ovarian cancer. (Nov.)

Zejula, an oral poly ADP ribose polymerase (PARP) 1 and 2 inhibitor, is marketed for adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers who have responded to platinum-based chemo. It is also in Phase III for breast cancer, and earlier trials for non-small and small cell lung, prostate, and brain cancers, as well as melanoma and Ewing’s sarcoma. Oregovomab, a high affinity monoclonal antibody, is designed to bind to the tumor associated antigen CA125 and is in Phase II ovarian cancer trials. OncoQuest will sponsor a Phase I/II trial of the Zejula/oregovomab combo, which will be partially funded by Tesaro. The study is expected to begin in 2018.

Pernix Therapeutics Holdings Inc.

SI Pharmaceuticals LLC

SI Pharmaceuticals LLC acquired Pernix Therapeutics Holdings Inc.'s third-generation cephalosporin antibiotic Cedax (ceftibuten) capsules and oral suspension for $2mm. (Nov.)

Cedax is a cell wall synthesis inhibitor for treating acute bacterial exacerbations of chronic bronchitis and middle ear infection. Pernix discontinued the drug in 2016. The company off-loaded the Cedax to SI so it can focus on its core CNS therapies including Zohydro for pain and the migraine drug Treximet. Pernix originally acquired Cedax from Shionogi Pharma for $6.1mm in 2010.

Portal Instruments Inc.

Takeda Pharmaceutical Co. Ltd.

Portal Instruments Inc. granted Takeda Pharmaceutical Co. Ltd. rights to use its needle-free drug delivery device with the Big Pharma’s GI mAbEnyvio (vedolizumab). (Nov.)

Portal gets undisclosed money up front and is eligible to receive up to $100mm in development, regulatory, and commercialization milestones, plus royalties. Portal’s device, licensed exclusively from MIT, delivers biologic therapies through a pressurized liquid instead a needle. The system reduces pain and anxiety commonly associated with needle-based drug delivery, and allows patients to self-administer at home. Takeda has been looking for a new way to administer Enyvio, which is currently delivered via intravenous infusion. The IV formulation of the drug is marketed for ulcerative colitis and Crohn’s disease; a Phase III trial is currently underway, investigation safety and efficacy of a subcutaneous form.

Principia BioPharma Inc.

Sanofi

Principia Biopharma Inc. granted Sanofi exclusive global rights to develop and sell its Bruton’s kinase inhibitor PRN2246 for multiple sclerosis and possibly other CNS conditions. (Nov.)

PRN2246 stands out from other BTK inhibitors in development due to its ability to cross the blood-brain barrier for greater access to immune cell and brain cell signaling, and is in Phase I trials for MS. Sanofi pays $40mm up front and up to $765mm in milestones, plus royalties. Principia can choose to co-fund Phase III studies in exchange for increased royalties or profit/loss sharing in the US. Principia chose Sanofi as its partner for PRN2246 following a competitive process; it believes the Big Pharma’s experience in the MS space will be advantageous to the continued development of PRN2246. (Sanofi already markets Aubagio (teriflunomide) and Lemtrada (alemtuzumab), and also has the anti-CD52 candidate GZ402668 in Phase II trials.) Principia plans to put the up-front money it receives from Sanofi towards continued development of another BTK inhibitor PRN1008, which is in Phase II for the skin-blistering disease pemphigus.

Puma Biotechnology Inc.

Specialised Therapeutics Asia Pte. Ltd.

Puma Biotechnology Inc. granted Specialised Therapeutics Asia Pte. Ltd. exclusive rights to sell the breast cancer therapy Nerlynx (neratinib) in Southeast Asia, including Australia, Singapore, Malaysia, Brunei, and New Zealand. (Nov.)

Puma stands to receive $4.5mm in up-front and milestone payments, plus double-digit sales royalties. Nerlynx is marketed in the US, but has not yet received regulatory approval elsewhere. Specialised Therapeutics is responsible for all regulatory activities and commercialization in its territories. The kinase inhibitor was approved by the FDA earlier this year as an adjuvant therapy following trastuzumab for adults with HER2-positive breast cancer. Specialised Therapeutics hopes to have approval in Australia by the second quarter of 2019. Nerlynx is the second breast cancer treatment in the company’s portfolio. It also sells Abraxane (nanoparticle albumin-bound paclitaxel) for metastatic breast cancer.

Financings

ADMA Biologics Inc.

ADMA Biologics Inc. (plasma-based therapies for primary immune deficiency disease (PIDD) netted $39.7mm through a public offering of 19.5mm common shares (including the overallotment) at $2.15. Proceeds will support manufacturing ramp-up, plasma fractionation facilities upgrades (remediation and build-out), regulatory activities related to the re-launch of IVIG product Bivigam, and continued development of Phase III PIDD candidate RI002. (Nov.)

Allena Pharmaceuticals Inc.

Allena Pharmaceuticals Inc. (treatments for rare metabolic and kidney diseases) netted $69.4mm through its initial public offering of 5.33mm common shares at $14, the low end of its intended $14-16 range. (Nov.)

Investment Banks/Advisors: Cowen & Co. LLC; Credit Suisse Group; Jefferies & Co. Inc.; Wedbush PacGrow Life Sciences

Alnylam Pharmaceuticals Inc.

Alnylam Pharmaceuticals Inc. (RNAi therapeutics) netted $784.9mm through the public sale of 6.44mm common shares (including the overallotment) at $125. Proceeds will support future commercialization activities surrounding patisiran (for hereditary ATTR (hATTR) amyloidosis with symptomatic polyneuropathy (previously known as familial amyloidotic polyneuropathy (FAP)); givosiran (acute hepatic porphyrias); and fitusiran (moderate or severe hemophilia A or B). (Nov.)

Investment Banks/Advisors: Barclays Bank PLC; Chardan Capital Markets; Credit Suisse Group; Goldman Sachs & Co.; JMP Securities LLC; JP Morgan Chase & Co.; Needham & Co. Inc.; Piper Jaffray & Co.

Apellis Pharmaceuticals Inc.

Apellis Pharmaceuticals Inc. (immunotherapies for autoimmune and inflammatory diseases) netted $139.5mm in its initial public offering of 10.7mm common shares at $14 on the NASDAQ. (Nov.)

Investment Banks/Advisors: Citigroup Inc.; Evercore Partners; JP Morgan & Co.

ArQule Inc.

In its second private placement in two months, cancer and rare disease drug developer ArQule Inc. netted $9.3mm through the sale of 8,370 Series A convertible preferred shares at $1,135; each preferred share converts into 1k common. Investors also received 2,260 four-year Series A preferred share warrants, which have a pre-conversion exercise price of $1,750 per share (or $1.75 per share post-conversion). Proceeds will support pipeline development, including work on lead candidates derazantinib (Phase III for intrahepatic cholangiocarcinoma and Phase Ia/IIb for solid tumors) and miransertib (Phase I/II for solid tumors and proteus syndrome). Pontifax group led the financing, and takes a newly-created seat on ArQule's board of directors. (Nov.)

Arsanis Biosciences GMBH

Arsanis Inc.

Arsanis Inc. (antibodies for infectious diseases) netted $42.8mm through its initial public offering of 4.6mm common shares (including full exercise of the overallotment) at $10 on the Nasdaq. The company had planned to sell 3.1mm shares priced between $15 and $17. (Nov.)

Investment Banks/Advisors: Citigroup Inc.; Cowen & Co. LLC; Piper Jaffray & Co. (Arsanis Inc.)

Arsanis Biosciences GMBH

Arsanis Inc.

Concurrent with the closing of its initial public offering, Arsanis Inc. (antibody therapies for infectious diseases) netted $18.6mm through the private placement of 2mm common shares at the IPO price of $10 to New Enterprise Associates. The company will use some of the proceeds for ongoing development of Phase II ASN100 for the preventing S. aureus pneumonia in mechanically ventilated patients and for other indications, and for preclinical candidate development. Citigroup, Cowen, and Piper Jaffray were the placement agents. (Nov.)

Investment Banks/Advisors: Citigroup Inc.; Cowen & Co. LLC; Piper Jaffray & Co. (Arsanis Inc.)

Assembly Biosciences Inc.

Assembly Biosciences Inc. netted $56.6mm through the public sale of 2.2mm common shares at $27.25. The company is developing treatments for hepatitis B and also for diseases associated with the microbiome (including ulcerative colitis, Crohn's, and NASH), and will use the offering proceeds to fund continued clinical and non-clinical studies and R&D. (Nov.)

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

Biophytis SA

Biophytis SA (therapies to restore the muscular and visual functions in diseases with unmet medical needs) raised €7.5mm ($8.8mm) through the private sale of 1.5mm ordinary shares at €5.00 each (an 18% discount). The company will use the funds to design a Phase II trial in orphan pediatric indications. Invest Securities and HC Wainwright were the placement agents. Biophytis raised €10.4mm in a PIPE just last month. (Nov.)

Investment Banks/Advisors: HC Wainwright & Co.; Invest Securities

Catalyst Pharmaceuticals Inc.

Catalyst Pharmaceuticals Inc. (therapies for chronic neuromuscular and neurological diseases) netted $54mm through the follow-on public sale of 16.4mm common shares (including full exercise of the overallotment) at $3.50 each. The company will use some of the funds for ongoing clinical trials of Firdapse (amifampridine/I-/ for myasthenia gravis (Phase II) and spinal muscular atrophy (Phase I), and for pre-commercialization activities for the candidate. (Nov.)

Investment Banks/Advisors: HC Wainwright & Co.; Piper Jaffray & Co.; Roth Capital Partners; SunTrust Banks Inc.

ChromaDex Corp.

ChromaDex Corp. (nutraceuticals) grossed $23mm in a private placement financing of 5.6mm common shares at $4.10 (slight premium to prior ten day market average) to venture capital and international strategic investors. The company plans to use the proceeds to accelerate international expansion and to drive its clinical research focused on solving aging. (Nov.)

Denali Therapeutics Inc.

Denali Therapeutics Inc. (neurodegenerative disease drug development) filed for an initial public offering of 8.33mm shares at a range between $17-19. (Nov.)

Investment Banks/Advisors: Evercore Partners; Goldman Sachs & Co.; JP Morgan & Co.; Morgan Stanley & Co.

Eleven Biotherapeutics Inc.

Eleven Biotherapeutics Inc. (developing targeted protein therapeutics mainly for cancer) netted $7.4mm through a public offering in which the company sold 5.5mm units at $0.80 (each containing one common share and a five-year warrant to purchase a share at $0.80) and 4.475mm pre-funded warrant units at $0.79 (with each unit consisting of one pre-funded warrant exercisable for one common share, and a five-year common share purchase warrant exercisable at $0.80). Proceeds will support development of lead candidate Vicinium, which is in Phase III trials for high-grade non-muscle invasive bladder cancer. (Nov.)

Investment Banks/Advisors: HC Wainwright & Co.

Entera Bio Ltd.

Israel-based Entera Bio Ltd. has filed for its initial public offering on the Nasdaq. (Nov.)

Investment Banks/Advisors: Oppenheimer & Co. Inc.

Erytech Pharma SA

Erytech Pharma SA (developing treatments for rare cancers and orphan diseases) netted $116.6mm through its US initial public offering of 5.4mm American Depositary Shares (including the overallotment; representing 5.4mm ordinary shares) at $23.26 apiece. The company already lists on the Euronext Paris following a $17.3mm IPO there in 2013. (Nov.)

Investment Banks/Advisors: Cowen & Co. LLC; JMP Securities LLC; Jefferies & Co. Inc.; ODDO BHF

Erytech Pharma SA

Erytech Pharma SA (developing treatments for cancer and orphan diseases) netted $17.1mm through a private placement of 791k ordinary shares (including the overallotment) at $23.26. The company issued the shares to investors in Europe and countries outside of the US and Canada concurrent with its initial public offering in the US. (The US IPO resulted in the sale of 5.4mm American Depositary Shares for net proceeds of $116.5mm.) (Nov.)

Fortress Biotech Inc.

Fortress Biotech Inc. netted $23.25mm in a stock offering of 1mm shares of Series A preferred stock at $25 per share. The preferred stock pays an annual dividend of 9.375% payable quarterly. The company will use the offering proceeds for R&D, to fund clinical trials, for manufacturing and supply costs of products, and to repay existing debt. (Nov.)

Investment Banks/Advisors: B. Riley FBR Inc.; HC Wainwright & Co.; National Securities Corp.

InflaRx GMBH

InflaRx GMBH netted $93mm in its initial public offering of 6.67mm common shares at $15 (mid-point of $14-16 filing range). The company had raised four prior rounds of venture funding including its Series D of $30mm just last month. (Nov.)

Investment Banks/Advisors: BMO Financial Group; JP Morgan & Co.; Leerink Partners LLC

Intellia Therapeutics Inc.

Intellia Therapeutics Inc. (CRISPR/Cas9 gene editing technology for drug development) netted $141mm through the public sale of 6.25mm common shares at $24. Intellia recently announced interim top-line data demonstrating first-of-its-kind liver genome editing using CRISPR/Cas9 delivered through the company's lipid nanoparticle formulation system. (Nov.)

Investment Banks/Advisors: Credit Suisse Group; Jefferies & Co. Inc.; Leerink Partners LLC

Leap Therapeutics Inc.

Leap Therapeutics Inc. (immuno-oncology) netted $17.3mm through a private sale of 2.96mm common shares at $6.085 (a 6% premium). Investors, including HealthCare Ventures and Eli Lilly, also received seven-year warrants to buy 2.96mm shares at the offering price. Raymond James and Ladenburg Thalmann were the placement agents. (Nov.)

Investment Banks/Advisors: Ladenburg Thalmann & Co. Inc.; Raymond James & Associates Inc.

Melinta Therapeutics Inc.

In conjunction with the closing of its acquisition of The Medicine Co.'s infectious disease business, Melinta Therapeutics Inc. entered into an agreement with Deerfield Management in which the private equity firm will initially provide $190mm in debt (six-year term with interest rate of 11.75%) and equity financing (giving Deerfield a 10% stake). An additional $50mm in debt is available to Melinta within 24 months of the acquisition close upon the achievement of $75mm in annualized sales measured on the basis of its most recent six-month business period. Melinta will use the financing to fund the $165mm up-front payment for the TMC business and to retire $40mm in debt. Deerfield will also earn a low-single-digit royalty on sales of TMC's antibiotic Vabomere when the drug exceeds $75mm in sales and ending when sales exceed $500mm. (Nov.)

Mirati Therapeutics Inc.

Mirati Therapeutics Inc. (developing oncology treatments targeted at genetic and epigenetic drivers of cancer) netted $86.5mm through a public sale of 2.9mm common shares (including the overallotment) at $13 and 4.14mm pre-funded warrants at $12.999. Mirati will use the proceeds to continue developing its non-small cell lung and solid cancer candidates sitravatinib (Phase Ib) and mocetinostat (Phase II), and other preclinical pipeline projects. (Nov.)

Investment Banks/Advisors: Barclays Bank PLC; Cowen & Co. LLC; HC Wainwright & Co.; Oppenheimer & Co. Inc.; SunTrust Banks Inc.

Motif Bio PLC

Antibiotics developer Motif Bio PLC entered into a $20mm debt financing with Hercules Capital. The first $15mm was drawn down immediately, and the remaining $5mm is contingent upon attaining certain milestones expected in 2018. The loan bears interest at 10% and is interest-only for a period of 15 months and extendable to 21 months on the achievement of certain milestones with a 30-month capital and interest repayment period thereafter. The company will use the proceeds for pre-commercialization activities of its acute bacterial skin and skin structure infection treatment iclaprim, which is expected to launch in the US in 2019. As part of the agreement, Motif issued Hercules warrants to purchase up to 73,452 of its American Depository Shares (each representing 20 ordinary shares) at an exercise price of $9.53 per ADS. In addition, Hercules can opt to participate in any subsequent financing up to $1mm. (Nov.)

Odonate Therapeutics LLC

Odonate Therapeutics LLC (cancer drug development) filed for its initial public offering on the Nasdaq Global Select Market. The company intends to sell 5.88mm shares for between $24-27 apiece. (Nov.)

Investment Banks/Advisors: Cowen & Co. LLC; Goldman Sachs & Co.; Jefferies & Co. Inc.

Orphazyme AS

Danish biotech Orphazyme AS (rare neuromuscular and lysosomal storage disorders) plans to offer up to 9.375mm new shares at a price range of DKK64-80 ($9.98-12.48) in an initial public offering on the Nasdaq Copenhagen Exchange. (Nov.)

Investment Banks/Advisors: Carnegie Investment Bank AB; Danske Bank AS; ODDO BHF

ProQR Therapeutics BV

Dutch biotech ProQR Therapeutics BV (rare diseases) netted $15.3mm through a public offering of 4.97mm ordinary shares at $3.25. The company will use the proceeds for ongoing development of Phase II QR110 for Leber's congenital amaurosis, preclinical QR313 for epidermolysis bullosa, and preclinical QRX421 for Usher syndrome. (Nov.)

Investment Banks/Advisors: HC Wainwright & Co.; National Securities Corp.

Puma Biotechnology Inc.

Puma Biotechnology Inc. (oncology) entered into a $100mm term loan agreement with Silicon Valley Bank and Oxford Finance. The company drew down an initial $50mm immediately and can access the remainder at its option and pending achievement of certain milestones. The loan matures on October 31, 2022. The money will support commercialization of Nerlynx (neratinib) as an adjuvant therapy for early-stage HER2-positive breast cancer, and will also be used to continue development of the compound in additional indications. (Nov.)

RedHill Biopharma Ltd.

RedHill Biopharma Inc. netted $21mm through a public offering of 4.1mm American Depositary Shares (representing 41mm ordinary shares) at $5.50 per ADS. The company develops and sells treatments for GI and inflammatory diseases and cancer; marketed products include Donnatal for IBS and acute enterocolitis, EnteraGam for chronic diarrhea, and esomeprazole strontium for GERD. (Nov.)

Investment Banks/Advisors: Cantor Fitzgerald & Co.; HC Wainwright & Co.; Nomura Securities International Inc.; Roth Capital Partners; SMBC Nikko Securities Inc.

SAGE Therapeutics Inc.

Sage Therapeutics Inc. (GABAA receptor modulators for CNS disorders) netted $283.5mm in a public offering of 3.5mm shares at $85. (Nov.)

Investment Banks/Advisors: Cowen & Co. LLC; Goldman Sachs & Co.; JP Morgan & Co.; Leerink Partners LLC; Morgan Stanley & Co.

Sarepta Therapeutics Inc.

Sarepta Therapeutics Inc. (rare neuromuscular diseases) netted $505mm through the private placement of $570mm aggregate principal amount (including full exercise of a $95mm overallotment) of seven-year 1.5% convertible senior notes to qualified institutional purchasers, including the company's CEO, who purchased $2mm worth of shares. (Sarepta upsized the deal from its original intent to offer $375mm in notes with a $75mm overallotment.) (Nov.)

Soligenix Inc.

Soligenix Inc. (rare disease-focused biopharma) netted $4.8mm in concurrent private placement and registered direct offerings. The company issued 1.6mm common shares at $2 (a slight discount to the prior 10-day trading average) in the registered direct offering and 982k common shares at the same price in a concurrent PIPE. Lead investors included Knoll Capital Management and ACT Capital Management and Aegis Capital was the placement agent. (Nov.)

Investment Banks/Advisors: Aegis Capital Corp.

Spero Therapeutics Inc.

Antibiotics developer Spero Therapeutics Inc. netted $77.7mm in its initial public offering of 5.97mm common shares (including partial exercise of the overallotment) at $14 on the Nasdaq. The company originally planned to sell 5mm common shares between $14 and $16 each. (Nov.)

Investment Banks/Advisors: Bank of America Merrill Lynch; Cowen & Co. LLC; Oppenheimer & Co. Inc.; Stifel Nicolaus & Co. Inc.

Synergy Pharmaceuticals Inc.

Gastrointestinal disease-focused Synergy Pharmaceuticals Inc. netted $52.6mm through the follow-on public offering of 21.7mm common shares at $2.58. The company also issued two-year warrants to buy 21.7mm common shares exercisable at $2.86. Synergy will use some of the proceeds to commercialize its Trulance (plecanatide) once-daily therapy for chronic idiopathic constipation. (Nov.)

Investment Banks/Advisors: Jefferies & Co. Inc.

Tesaro Inc.

Tesaro Inc. (cancer therapeutics) entered into a $500mm term loan agreement with Biopharma Credit PLC and Biopharma Credit Investments IV (both managed by Pharmakon Advisors). Tesaro will draw down the first $300mm in early December, and the company has until December 20, 2018 to draw on the remaining $200mm. Both tranches will mature on the seven-year anniversary of the first draw-down date; the initial installment carries interest at a rate of LIBOR plus 8%, while the second will be at LIBOR plus 7.5%. Both are secured by security interests in IP related to Tesaro's Varubi (rolapitant; chemo-induced nausea and vomiting) and Zejula (niraparib; recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer), and by additional equity interests and cash on hand. (Nov.)

The Medicines Co.

Concurrent with The Medicine Co.'s divestiture of its infectious disease business to Melinta Therapeutics Inc., Deerfield Management has provided TMC with a $100mm loan that bears an interest rate of 5% per annum and, if drawn upon, will mature on the earlier of either the closing of the Melinta transaction or one year. (Nov.)

Vascular Biogenics Ltd.

Vascular Biogenics Ltd. (VBL; mainly oncology therapeutics) netted $17.9mm through a public offering of 2.5mm common shares at $7.20. The funding comes ten days after VBL granted NanoCarrier exclusive Japanese rights to lead solid tumor candidate VB111 (ofranergene obadenovac). Through that deal, VBL gets $15mm up front and up to $100mm in milestones, plus royalties. (Nov.)

Investment Banks/Advisors: Piper Jaffray & Co.

Vical Inc.

Vical Inc. (infectious disease therapies) netted $23.3mm through a public offering of 7mm common shares at $1.75 and 7.2mm pre-funded warrants at $1.74. Proceeds will support clinical trial expenses related to the company's projects for cytomegalovirus, herpes simplex virus type 2, and fungal infections. (Nov.)

Investment Banks/Advisors: HC Wainwright & Co.

Voyager Therapeutics Inc.

Voyager Therapeutics Inc. (neurological disorder AAV gene therapies using gene replacement or gene knockdown) netted $50.8mm in a public offering of 4.5mm shares at $12. The 2014 start-up will use the proceeds to fund development of its pipeline, which includes lead candidate VYAADC, in Phase Ib for Parkinson's disease. (Despite recent news that Genzyme would not exercise its option under a 2015 deal to exclusively license ex-US rights to the compound, Voyager is proceeding with a pivotal Phase II/III trial for VYAADC expected to begin in Q2 2018.) The company also has multiple preclinical programs in pain and neurodegenerative diseases, including ALS, Huntington's disease, Friedreich's ataxia, frontotemporal dementia, and Alzheimer’s disease. (Nov.)

Investment Banks/Advisors: Cowen & Co. LLC; Morgan Stanley & Co.; Nomura Securities International Inc.; Stifel Nicolaus & Co. Inc.; Wells Fargo Securities LLC