On Jan 24, 2024, SDEE hosted another successful Get To Know Your Neighbors (GTKYN) event at Green Acre in San Diego. Thanks to all SDEE’s sponsors for their continuous support: Morrison & Foerster, Alexandria, BDO, Kyowa Kirin, Johnson & Johnson, Takeda, CBRE, Fifth Third Bank, Longfellow, Scientisit.com, Marsh & McLennan, Duane Morris, Union Bank, Wagenknecht Law Group, and Pater Pallai.

Lots of exhibitors and attendees mingled during the opening reception with drinks, tiny tostadas, and delicious pizza before the current SDEE president, Marilyn Ferrari, introduced the new president, Janelle Hunt. Congratulations and best wishes to Janelle!

Photo: Janelle Hunt, SDEE President

After 15 companies gave the traditional 30 second pitch, Mike Grey took the stage as the keynote speaker.

Mike focused his talk on four companies, two that he founded - Lumena and Mirum - and two that he helped grow - BioMarin and Horizon.

Full circle with Lumena and Mirum

Mike decided to start his entrepreneurial career in 2010 with clinical stage compounds that had been discontinued by big pharma companies, as repurposing compounds for rare diseases seemed the best opportunity for success. In particular, the idea for Lumena was born when the founder of Amylin proposed to work on an ileal bile acid transporter (IBAT) inhibitor for type 2 diabetes. Instead of this indication, Mike decided to pursue this mechanism of action for liver diseases.  He identified 6 IBAT inhibitors and engaged 4 pharma companies. Most big pharma do not have an out-licensing team, and the process can be lengthy. Eventually, with the $500,000 he was able to raise, he in-licensed maralixibat and volixibat, which had been discontinued by Pfizer and Sanofi, respectively. He opened a windowless office on High Bluff Drive, raised $23 million in series A in June 2012, and initiated phase II studies in adult and pediatric patients with rare cholestatic liver diseases. Importantly, patient advocacy groups helped design the studies and define outcomes based on what is important to the patients. Although not everybody responded to these drugs, the efficacy was remarkable in some patients, with reduction of debilitating itch and scratching, better night’s sleep, and better liver function. Lumena was about to go public when it was acquired for $260M upfront in 2014 by Shire. Initial phase II studies sponsored by Shire were not successful at least in terms of statistical significance, possibly because of the large placebo effect and the dose not being optimized. However, the clear efficacy signal led a randomized withdrawal study, initially designed by the Lumena team, with higher doses. In the ICONIC study, all patients started on maralixibat and, after 18 weeks, were randomized to continue on the drug or switch to placebo. Unfortunately, Shire announced in 2016 that maralixibat again had failed to meet its primary endpoint. Even if some patients responded very well and the compound received breakthrough therapy designation, the interest in maralixibat faded when Shire merged with Baxalta. In 2018 Mike gave maralixibat and volixibat yet another chance by reacquiring them and founding Mirum. Maralixibat (Livmarli) was approved by FDA in Sept 2021 without the need of a phase III trial for treatment of rare cholestatic liver diseases, such as Alagille syndrome, progressive familial intrahepatic cholestasis, and biliary atresia. Mirum is continuing to work on volixibat and also commercializes chenodiol (Chenodal) and cholic acid (Cholbam) acquired from Travere.

Photo: Keynote Mike Grey

Different leadership at BioMarin and Horizon

Mike is and has been on the board of other companies, including BioMarin and Horizon. Both companies had great teams, science, culture, and products, but different leadership approaches. BioMarin was very science focused and grew to a $2 billion valuation without turning a profit, while Horizon’s early focus profitability drove the optimization of its compounds’ commercial potential. Both companies are very successful, but Horizon had a better financial position and was acquired by Amgen for $23.2B.

Final thoughts

Even if it is a brutal business and phase III failures are common even if everything is done correctly, the acute focus on the patients who benefit from the drugs and on building strong teams is what makes companies successful. After all, venture capitalists invest in people and teams first, and products second.