Amira asset DP2 blockers spun out, not part of BMS $325 million buyout
This article was originally published in Scrip
Just prior to Bristol-Myers Squibb wrapping up its buyout of San Diego-based Amira Pharmaceuticals, the company spun out certain assets that were not part of the deal into two separate companies.
BMS acquired only certain Amira research programmes (including a fibrosis programme) for $325 million cash up front plus $150 million in future milestones. But there were other assets in Amira that BMS chose not to acquire, because it said they were not a strategic fit or not in their core interest area (scripintelligence.com, 22 July 2011). With the announced spin-outs, the fate of those assets has now become known. Two independent companies have been set up for former Amira shareholders, established as limited liability corporations (LLCs), and these will carry the spun-out programmes forward.
The first spin-out, Panmira Pharmaceuticals, will hold candidates for inflammatory diseases from the former Amira. The main concern of this start-up will be completing the task of partnering the asset to big pharma or some other partner so that they can continue with the development work. There is currently no plan for additional basic research on the part of Panmira, but that could change in the future. Amira's former chief executive Bob Baltera is heading up Panmira, and Dr Hari Kumar, who has also been with Amira for several years, is serving as chief business officer. The company will have just a handful of former Amira employees. If it needs to bring in additional resources for any reason, it plans to turn to part-time consultants.
Amira's shareholders are also holding onto to the rights to future milestones and royalties for the firm's inhibitors of 5-lipoxygenase-activating protein (FLAP) – a programme which is involved in a 2008 licensing pact with GlaxoSmithKline. These rights will be held through a non-operating LLC which will be known as FLAP LLC. The lead programme for FLAP, AM103/803, advanced to Phase II studies in asthma last year.
Panmira, which will be headquartered in San Diego, will have a progamme of novel DP2 antagonists, which have shown efficacy in mouse models of chronic obstructive pulmonary disease (COPD) and asthma. Two candidates, AM211 and AM461, have been investigated in humans in Phase I trials.
There are no DP2 selective antagonists approved for therapeutic use.
In announcing the formation of the new company, Dr Kumar said in statement, "Clinical trial results have demonstrated a dose proportional pharmacodynamic effect and good safety profiles for both AM2121 and AM461. These compounds are primed and ready for Phase II exploration in a number of clinical settings, including asthma, COPD and eosinophillic esophagitis. We look forward to having the right partner to help make these plans come to fruition."
Dr Kumar told Scrip that key members of the Amira team are excited that the spin-outs have come to fruition. In describing the new arrangement, he said, "It means for us keeping the value that we have build into those assets, and being able to do something with them".
For AM211 and AM461, Dr Kumar described how the company has been able to go beyond the normal Phase I concerns of safety and pharmacokinetics in healthy volunteers – and measure pharmacodynamic markers alongside that data. The data so far clearly show that there is in vivo efficacy for the compounds, and that the compounds are essentially Phase IIb ready, he said. He was quick to point out, however, how a Phase II study in the respiratory area would be too much of a hurdle for a small company.
Dr Kumar described some of excitement surrounding DP2 antagonists. "We are not alone in the research," he said. "A number of people have been studying this target and identified that one of the key things that this target does is it has a particular effect on eosinophils, and one can take blood from healthy volunteers and measure the change in the eosinophils, and its called the eosinophil shape change because when the target is bound to the antagonist the eosinophils take on a morphological change – the biology of it is that essentially this target is part and parcel of a process in which the eosinophils migrate from the blood vessels into the area of damage, or the area of inflammation."
He went on to state, "So one can measure the morphological change and inhibition of the morphological change by the antagonist – a sort of neat pharmacodynamic biomarker."
Dr Kumar claimed that Amira was the first to publish work showing that inhibition of this particular receptor has an effect on neutrophils. In what is known as a smoking mouse model, the compounds can inhibit migration of neutrophils into the lungs, and neutrophils in the lungs have been linked to a number of pathologies including COPD.
Panmira says that DP2, also known as a chemoattractant receptor-homologous molecule expressed in Th2 lymphocytes (CRTH2), is a high affinity receptor for the prostaglandin D2 and is implicated in humans in Th2-dependent allergic inflammation. Prostaglandin D2 seems to play a role in asthma and allergic diseases.
Dr Kumar said that others working in the field have not published a lot of data thus far, but that some work on some major studies may be published in the near future. These data hopefully "will support the fact that this target has a role to play in not just respiratory diseases but in a number of inflammatory conditions".
As for the business side, Dr Kumar said that essentially all of the shareholders transferred their holdings of the remaining assets into Panmira and FLAP. "We are not intending to raise new capital or new investment – hence the reason they are LLCs", he said.
He added, however, that if a potential partner wanted to see some more data, it could be provided through contractual work. "We certainly don’t feel at this time that we'll be engaged in some major task of data generation."
Amira's shareholders include Avalon Ventures, Novo A/S, Prospect Venture Partners, and Versant Ventures.