Acacia Pharma Raises $23.5 M Series B For Repurposing Drugs As Anti-Emetics
This article was originally published in The Pink Sheet Daily
Executive Summary
Other product candidates in the cancer supportive care sector being developed by the U.K. virtual biotech include a liquid formulation of a muscarinic agonist for dry mouth and a megestrol/formoterol combination therapy for muscle wasting.
U.K. repurposing biotech Acacia Pharma Ltd. has raised £15 million ($23.5 million) in a Series B round to fund completion of the Phase III development of APD421, its lead product for post-operative nausea and vomiting (PONV). Other companies already market the active ingredient in APD421 in a CNS indication.
The fundraising, which comes two years after the Cambridge-based virtual company raised $10 million in a Series A in March 2011, adds two new VCs to its investor group – Fidelity Biosciences and Novo A/S (Also see "Financings Of The Fortnight Notes A Rarity, Big Funding Rounds In Europe" - Pink Sheet, 1 Apr, 2011.). The funds extend Acacia's cash runway out to the middle of 2015 and are enough to complete Phase II studies of the company's second pipeline product, APD403, for the prevention of chemotherapy induced nausea and vomiting (CINV).
"The new investors add to our Series A venture capital investors, Gilde Healthcare and Lundbeckfond Ventures, who also contributed to the Series B," said Acacia's CEO Julian Gilbert. Although the company plans to find marketing partners for its products at the end of Phase III, the strength of its financial backing means Acacia could consider commercializing its own products, he said.
Gilbert is no stranger to repurposing medicines, having co-founded and been commercial director of Arakis, a U.K. company with a similar repurposing strategy that was sold to Sosei Co. Ltd. in 2005 for £107 million [See Deal]. Arakis and fellow U.K. biotech Vectura Group PLC collaborated on the repurposing of the muscarinic antagonist, glycopyrronium bromide, for chronic obstructive pulmonary disease (COPD). This is now marketed by licensee Novartis AG as Seebri Breezhaler (Also see "EU's CHMP Gives Green Light To Three New Products And A New Indication For Afinitor" - Pink Sheet, 22 Jun, 2012.).
Glycopyrronium is widely available generically in various formulations to reverse neuromuscular blockade, or to reduce salivation or sweating. Another example of a repurposed medicine is thalidomide, now marketed for multiple myeloma (Also see "Celgene To Launch Pomalyst At $10,500 Per Treatment Cycle" - Pink Sheet, 8 Feb, 2013.). There has been renewed interest in repurposing compounds, particularly those abandoned during development, including a pilot U.S. National Institutes of Health program and various programs being undertaken by pharmaceutical companies (Also see "AstraZeneca Has Stake In Three Of Nine NCATS Research Projects" - Pink Sheet, 18 Jun, 2013.).
"One of the core competencies in the repurposing area is obtaining strong intellectual property (IP) protection on the new medicine, through use patents and other means," Gilbert explained in an August 29 interview. Other IP can include formulation and process patents, he said.
Acacia identified cancer supportive care as an area with unmet medical needs that could be addressed by repurposed products, Gilbert said. Advantages of this approach include being able to move rapidly to the clinical proof-of-concept stage, and being cash efficient. Acacia only has three full-time employees, but supplements these with a network of contract research organizations, contract manufacturers, and business and regulatory consultants.
Dopamine Antagonist
Lead project APD421 is an undisclosed dopamine D2/D3 antagonist, currently marketed by other companies in a CNS indication, which has shown to have potential in the treatment of PONV in Phase II studies conducted by Acacia, Gilbert said. APD421 is a very low-dose intravenous formulation of the marketed product, and Acacia is about to start two pivotal Phase III studies with the product.
"In PONV, there is still an unmet need for a more efficacious product. Surgical patients have to be re-admitted to hospital because they cannot stop being sick after an operation," Gilbert noted. The aim with APD421 was to develop a medicine with the efficacy of droperidol, but without the QT prolongation issues associated with that product.
In 223 post-surgery patients at risk of PONV studied in a Phase II dose ranging study, the optimal dose of APD421 was associated with a halving of the PONV rate, from 67% in the placebo group to 36% in the APD421 treated patients. The incidence and severity of nausea was also significantly reduced.
The company's second pipeline product, APD403, is a slightly higher dose of the same active ingredient as that in APD421 and which is being developed in intravenous and oral formulations for the treatment of CINV. "Although there are a number of efficacious drugs marketed for CINV, it is often difficult to suppress nausea, particularly in the delayed phase of CINV," Gilbert said. In Phase IIa studies, APD403 has shown potential as an antinauseant and further Phase II studies are planned.
A third product, APD515, is a muscarinic agonist which is being evaluated in a liquid formulation for the treatment of dry mouth (xerostomia). Current muscarinic agonists are marketed as tablets, but liquids are probably easier for xerostomia patients to take, Gilbert said.
Acacia also has some interesting preliminary data on a fourth product, APD209, an oral fixed-dose combination of megestrol and formoterol, which has shown potential in the muscle-wasting condition, cachexia. But the company wants to take this forward with a third party, given the complexities of developing products for this indication, Gilbert said.