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NIH and Disc Medicine Partner to Help Bring Anemic Patients Out From the Shadows
By Sarah Ellinwood
March 30, 2023
Millions of people around the world live with some form of anemia, characterized broadly as a condition where a person has a lower-than-normal level of red blood cells. Despite this high number, though, many don’t understand what anemic individuals go through or the burden the disease has on their daily lives.
At face value the symptoms don’t seem all that bad – fatique, pale skin, maybe shortness of breath from time to time. Those symptoms, though, have a huge impact on how a person lives their day-to-day. Normal activities, such as cleaning around the house or walking the dog, become a huge struggle. You rarely have the energy to meet up with your friends for something as simple as brunch. Having an office job isn’t realistic because the commute alone completely drains you.
For many, living with chronic anemia is akin to living in the shadows.
And compared to other diseases such as inflammatory diseases and cancer, treatment options are archaic. Your main options are going to the doctor on a regular basis for blood transfusions or taking steroids. Stem cell transplants can serve as a last resort, but are risky.
Disc Medicine, based in Watertown, MA, is extending a hand to help bring patients with anemia and other hematologic diseases out from the shadows to live more normal lives. And their recent partnership with the National Heart Lung and Blood Institute (NHLBI), a branch of the NIH in Bethesda, Maryland is extending that reach even further.
Through the partnership Disc will be launching a Phase II clinical trial evaluating one of their lead assets, bitopertin, in patients with Diamond-Blackfan anemia (DBA). DBA is a rare genetic disorder resulting in the person’s bone marrow not being able to produce enough red blood cells. The disease usually presents in infancy or early childhood – in addition to typical anemia symptoms, children also might have a smaller head size or malformed fingers. While patients can live long and healthy lives with appropriate treatment, that treatment is also lifelong.
Bitopertin is an orally-administered drug that inhibits GlyT1, a membrane transporter that plays a key role in the production of red blood cells (erythropoiesis). Disc licensed bitopertin from Roche in 2021 – Roche was initially developing the drug to treat schizophrenia, but it failed to meet its primary endpoints in Phase III trials. Now, based on its mechanism of action, it’s seeing a new light as a potential therapeutic to treat hematologic diseases.
Further, because bitopertin’s safety and tolerability had already been shown in Roche’s previous trials, Disc could go straight into Phase II, meaning this investigational therapy could potentially enter patients’ hands quicker.
“Bitopertin presented a very attractive profile to us, and we set out to understand what range of human disorders we might be able to address using this molecule,” John Quisel, JD, PhD, CEO at Disc Medicine, told BioBuzz. “We have a Phase II in erythropoietic protoporphyria already underway. The concept of looking at Diamond-Blackfan anemia was generated by a group of researchers at the University of Washington in Seattle. We had followed that thread and started a collaboration there to explore whether bitopertin could address the excess heme synthesis and buildup that resulted in toxic concentrations in new red blood cells.”
Meeting patients where they’re at
“The collaboration was going really well, and as we were working with the University of Washington it came to our attention that at the NIH there are several research teams exploring ways to treat this really terrible disorder. They have a population of patients who’ve been generous with their time and willing to participate in clinical trials that the NIH has administered over the years,” Quisel added.
As Disc and NHLBI began talking to one another, an opportunity arose. It so happened that there were a few ongoing clinical trials winding down, giving Disc an opening to see if bitopertin could help these patients. Recruitment is always a concern when it comes to clinical trials, and for those investigating in the rare disease space the hurdle is even higher. Forming a partnership where the patients are at already just makes sense.
“The collaboration came together fairly efficiently – under a year for sure,” said Quisel. “We were pleasantly surprised – I think it has to do with the really high motivation and eagerness to bring new options for this group of patients at the NIH. They worked really heard to push this ahead. And for us we already had the molecule in hand for our other clinical trial. It was fairly easy for us to divert supply to this trial. That combination of enthusiasm on both sides to chase what we think is really compelling science – the circumstances all came together well.”
When open, the Phase II study will be a pilot, single-arm, dose-escalation trial in DBA patients who either have steroid-refractory and/or relapsed disease or are unable to tolerate systemic corticosteroids. The study includes planned dose escalation within each participant to continually assess for hematologic response.
If the trial goes well and bitopertin shows signs of efficacy, the team will next think about structuring a subsequent trial involving multiple centers, potentially worldwide.
A beacon of light amongst rough waters
You know it. We know it. The once roaring COVID-fueled biotech economy with IPOs and SPACs abound has simmered down into embers, with new companies reprioritizing their portfolios and laying off employees everyday.
Despite the circumstances, Disc Medicine has braced the storm fairly well so far. The team has initiated a handful of clinical trials in multiple indications both for bitopertin and for one of its other assets, DISC-0974, with some initial data expected by the middle of the year. The company also obtained exclusive rights to Mabwell Therapeutics’ MWTX-003 and other novel Anti-TMPRSS6 monoclonal antibodies at the beginning of 2023, with plans to initiate a Phase I trial in healthy volunteers the second half of the year.
Funding-wise, just last month Disc announced a $62.5 million financing round let by Bain Capital Life Sciences, which followed the company’s merger with Gemini Therapeutics at the tail end of 2022.
In a time where some startups are scrambling, we were curious as to how Disc was not only holding steady, but forging forward.
“We’ve worked really hard continuously trying to produce that next piece of data to help demonstrate the the science we’re doing is going to make a difference,” said Quisel. “And then that feeds into the story and what we’re able to show potential investors. It has been, no doubt, exceptionally challenging in the face of so many different obstacles, between COVID, interest rates, and inflation. The latter two really damaged the interest in biotech investment. We were able to push through that by being able to show the encouraging data coming from our trials and our studies.”
He added, “We have also looked at everything. We have talked to anyone who has an ability to work with us or help potentially fund what we’re doing. We’ve met with them. We’ve talked to them. We look under every rock we can to get us to that next step, get that next experiment done, and progressing.”
As for Disc and NHLBI’s newest partnership, it goes to show the importance and potential opportunity of every conversation and collaboration.
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Sarah Ellinwood is BioBuzz’s Managing Editor. A scientist by training and a science communicator at heart, Sarah specializes in making complex concepts understandable, engaging, and exciting. She received her Ph.D. in molecular and cellular biology with a focus in infectious disease immunology from the University of Maryland and is passionate about all things related to scicomm, peer mentorship, and women in STEM.
