To preface, Allena Pharmaceuticals (ALNA) has a Phase 3 readout coming in Oct/Nov 2019 for its lead product, Reloxaliase, in enteric hyperoxaluria. It’s a crystalline formulation of an enzyme, oxalate decarboxylase, designed to break down oxalate – a molecule that humans cannot break down, but absorb from foods we eat and endogenously produced mostly by the liver. Too much absorption or production can lead to calcium oxalate stones (kidney stones) and lead to end stage renal disease. But where did this drug and enzyme therapy idea come from?
The story begins with Alexey Margolin, the co-founder, and now the Chairman of the Board of ALNA. From 1993-2007, he was CSO at a company called Altus Therapeutics. Margolin was in charge of a product called liprotamase, which started development on in 2001 in collaboration with the Cystic Fibrosis Foundation (CFF). Also known as Trizytek (and later Sollpura), liprotamase was a porcine-free pancreatic enzyme therapy for cystic fibrosis patients with pancreatic insufficiency. The company finished several smaller trials, but ran into financial difficulties and discontinued development mid Phase 3 trial. The CFF then looked for another partner to finish the drug and hopefully bring it to market.
Just before this, Margolin had left Altus, and formed Alnara Pharmaceuticals in 2008 with a $20m Series A backed by Frazier Healthcare (James Topper), Third Rock (Robert Tepper), and Bessemer Ventures. Margolin saw the opportunity to work on liprotamase again, and licensed the rights from CFF in 2009. Alnara quickly went from a 1 person shop to hiring 20 people in the next 10 days. The Phase 3 trial finished, but liprotamase did not show as much efficacy as hoped. Still, Alnara raised another $35m in a Series B to submit the drug to the FDA. In 2010, Eli Lilly purchased Alnara (later revealed to be $180m upfront, up to $380m), rewarding early investors. However, not all went well for LLY, as the drug went on to be rejected by the FDA. Years later in 2014, Anthera would purchase the rights, run another Ph3, ultimately be rejected again in 2018, and would finally discontinue development of the drug.
Concurrently, Altus had shifted focus to its growth hormone formulation, finished a Phase 2 trial, but ran into the death spiral commonly seen in small biotechs. Running out of cash again, Altus was purchased by Althea Technologies in 2010 (Althea was then purchased by Ajinomoto for $175m in 2013). The early growth hormone data showed relevant PK/PD for once-weekly injections, but the company lacked any funding to move it to a larger trial (especially after Genentech pulled their collaboration). Along with the GH asset came Altus’s Cross Linked Enzyme Crystal (CLEC) IP. CLEC was intended to allow enzymes to remain active in otherwise incompatible environments, such as high temperatures, or extremes of pH. In 2009, Altus ran a preclinical trial of a CLEC formulation of oxalate decarboxylase (OxDc-CLEC) that showed lowering of urinary oxalate in animal models.
What became of Margolin after Alnara’s acquisition? He moved on to start two companies. One was Alcresta in 2012, also in the field of enzyme therapies, backed by Bessemer, Frazier, and Third Rock in a $10m Series A. Alcresta would form a collaboration with the CFF in 2013. The other was Allena in 2011, backed by Bessemer, Frazier Healthcare (James Topper), and Third Rock (Robert Tepper) with a $15m Series A. In 2012, Allena then licensed rights to the hyperoxaluria portfolio from none other than Althea Technologies (making this a lovely full circle). Of note, Reloxaliase seems to be a slightly different formulation. ALNA emphasizes that it is an uncrosslinked version of oxalate decarboxylase, which seems to have a higher activity in more acidic pHs, but perhaps is more susceptible to proteolytic degradation in the GI tract. To date, ALNA has run several smaller trials in hyperoxaluria. Does it work? Sort of, but more on that in Part 2.
If you’re confused with this history like I was, I drew you a crude diagram to illustrate how all this went down.
MS Biotech Thoughts 