A Biotech Outsourcing For Sickle Cell Anemia
By Louis Garguilo, Chief Editor, Outsourced Pharma
Most CEOs are excellent communicators. In our industry, they’re particularly good at describing their development strategies, pipelines, and commercial products.
Many are so good, shall we say, they easily slip into public-relations rifts, intriguing investment pitches, and some downright advanced advertising.
With Rahul Ballal, CEO, Imara, Inc., you get all the first part (clear communication) without any of the latter (ballyhoo).
That’s why his steadfast tale of an incubator-bred biotech, and its small-molecule program for sickle cell anemia, is so informative and relatable.
It’s very much a narrative of drug development and manufacturing outsourcing, and how some 40 employees handle a supply chain feeding global (and numerous) clinical trials and distribution needs.
Incubated, Incorporated, In-progress
Incubated
The company started as a virtual organization and continues to selectively outsource key functions.
According to Ballal, ingrained between 2016 and 2018 is that smart outsourcing is much more than a relevant strategy, “but a key fabric in scaling the company quickly and efficiently.”
However, he says, that growth must be matched by a combination of talented internal employees, local support presence, partnerships with vendors, and good oversight of it all.
The accelerator was Cydan, an NEA-backed venture in Cambridge, Mass. Its thesis is to advance to proof-of-concept years quicker than normally required.
To meet that objective, a series of initial experiments are designed, depending on molecule stage. In Imara's case, it was right to IND-enabling experiments, which were all outsourced to a number of service providers.
“Putting together the IND and entering the clinic was the job of the dedicated Cydan team,” says Ballal. “Once in the clinic, it was the company’s job to ‘take over.’”
The molecule Imara formed around was brought in from Lundbeck, who had been developing PDE9 inhibitors for CNS indications, but that ultimately failed. “They put the entire class on the shelf,” explains Ballal. “Imara did some work on other indications where PDE9 inhibitors could be viable. In sickle cell, PDE9 is highly overexpressed so an inhibitor has better chance at demonstrating a therapeutic effect.”
That lead candidate is IMR-687, an oral, once-a-day, highly selective, potent small molecule, now in phase 2b clinical development (more below).
“Over that period in the accelerator,” says Ballal, “we did exactly what small companies do: negotiate to get assets out of big pharma and into our hands, and quickly take action to develop them.”
Incorporated
“I came in mid-2018 and hired a small staff,” he continues. “We financed the company, with the help of a strategic CFO, Mike Gray, and did an IPO. We got some phase 2a data in sickle cell, and have expanded to other indications, including beta thalassemia and heart failure with preserved ejection fraction.”
A few months later, Imara moved out of the incubator and headquartered in Boston – with no lab space.
“We decided it was more efficient to keep key elements of the outsourcing model in place. We hired a team of strong project managers, clinical operations leaders, and then the relevant physicians and regulatory people to compliment what we were doing on an outsourcing basis.”
What Imara was doing was to continue to build up global outsourcing relationships to help run clinical studies and provide supply to approximately 90 sites across two different programs in a total of 15 countries.
“Smart outsourcing across drug manufacturing to clinical trials and operations has provided us scale, even though we remain a small biotech says Ballal.
In-progress
The growth philosophy at Imara – one not universally shared in our industry – is to proportionately add internal resources as outsourcing needs progress.
“A great example of that would be what we're doing in CMC, or in terms of drug substance and drug product,” says Ballal.
“We've hired a CMC team, including a dedicated person in drug product and one in supply chain to manage a number of vendors to get the drugs to the right places. We have a person in drug substance to manage those vendor relationships, but also continue to improve the drug substance. Overall, we've selectively hired in those categories that help not only manage the vendor, but manage the program as it matures. It helps that our CDMO partner has been excellent, and at times, served as a de facto internal employee, putting on the Imara hat as we discuss strategy and options.”
Go All The Way
I ask Ballal to pull this narrative into the future. Is there an exit strategy of some kind – a Big Pharma sale of the key asset(s), or sale of the company, should commercial approval be achieved.
He replies by pointing to the success of another company, Global Blood Therapeutics (GBT), and its drug (Oxbryta) for sickle cell disease. GBT appears to maintain a relatively small sales force, while in the first half of 2021 generating sales worth an estimated $86.6 million, according to public documents.
“For us, there are only about one-hundred-thousand patients in the U.S., so we are committed to taking this drug all the way there,” says Ballal. “It's an oral, once-a-day requiring no refrigeration, or any fancy anything.”
“We are running our phase 2b study largely outside the U.S., in very different climates. There're many attributes that make it easy to commercialize, as opposed to maybe a gene therapy drug.”
And while sickle cell is a rare disease in the U.S., 4 million people are afflicted worldwide. Access is an issue for people in less developed countries.
“What's the best way to reach them? It's a daily oral that comes out of a bottle – with no titration or monitoring required.
“That’s why we’ve worked to maintain our flexibility as a company to take our program forward,” he says.
“Yes, we have to dispense the drug in many locations. So we got help with package labeling and depots. We went with a large provider with a footprint across the world – the last mile, as they say. It didn’t make sense to select someone smaller, because, for example, in a Tunisia or a Uganda, it's already hard enough. Partnering with a global provider that subcontracts out and has real experience in those countries is helpful.”
Ballal continues: “But with supply, we've gone in the opposite direction – a CDMO with a small but capable footprint in North Carolina. They have a very good, dedicated group allowing us the flexibility to get manufacturing slots in acute times.
“We have our API made in China, but thought it important to have it shipped from China to North Carolina immediately for storage.”
All setting up nicely for the long haul of commercialization. The narrative is positive, but I detect no posturing from this CEO; just a biotech effectively utilizing outsourcing to tackle an important disease target.