Due to launch in the second half of this year, Rallybio Inc.’s phase I/II study testing RLYB-211 for prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT) will begin with experiments in men, said Steve Uden, one of the company’s three founders. “The good news is, we can confirm the safety and the pharmacology of this concept in male volunteers before having to start a clinical trial in pregnant mothers,” he told BioWorld.
New Haven, Conn.-based Rallybio wrapped up a $145 million series B financing for a portfolio led by plasma-derived hyperimmune globulin RLYB-211 against FNAIT, a rare disease that affects several thousand pregnancies a year and may cause death in utero or in the course of delivery. Intracranial hemorrhage is another grim possibility.
FNAIT is caused by a mismatch of antigens between the fetus’ platelets and those of the mother. About 98% of Caucasians have antigen on the surface of their platelets called HPA-1a, Uden said. In cases where the mother is HPA-1a-negative and the fetus is positive, if the blood of the two mixes – which can happen for various reasons – the mother can raise antibodies against the fetus’ platelets and may do so “at titers high enough that the antibodies cross in large amounts into the fetus’ circulation [and] take down the platelets, so [the fetus] is then at risk of all these thrombocytopenic complications,” he said.
RLYB-211 works by way of antibody-mediated immune suppression, a long-known mechanism. “If you give the antibody that causes the problem itself at a very low dose, too low to cause problems in the fetus, it causes a targeted immunosuppression such that the mother will not react to the baby’s platelets,” Uden said. Testing the compound, which Rallybio licensed as NAITgam from Prophylix A/S, of Tromso, Norway, first in men is meant to take away some of the risk. “We will find men who are HPA-1a-negative,” he said. “They will be given a full dose of HPA-1a-positive platelets, simulating a fetal bleed,” followed by RLYB-211. Rallybio will measure “what we predict will be a rapid disappearance of platelets,” he said. “If I were to infuse platelets into a volunteer, they would survive in circulation for about two weeks. We expect that this therapeutic will clear them within a matter of hours.” Volunteers also will be followed to confirm that they don’t seroconvert and produce antibodies. Prophylix, he said, did “outstanding work in terms of producing preclinical models” and exploring the fundamental biology. “It was a natural handoff,” to a drug development firm such as Rallybio.
Diagnosis of FNAIT can be done by way of a simple blood test, Uden said. “If the mother is HPA-1a-negative, the next thing would be to do fetal DNA sampling, which is now becoming quite routine.” All the necessary diagnostics already are available, he noted. Pregnant women reliably consult their doctors as soon as they realize their condition, he noted, and a blood test happens promptly. “At the moment, [FNAIT] is not routinely screened for, because there’s no way of preventing it,” he said, citing “a rather fatalistic view that there is no point in looking for something you can’t do anything about,” though Europe has done epidemiological screening, and some has taken place in the Netherlands. If RLYB-211 wins approval, the HPA-1a test “would be added to that battery of tests done at the very first visit” by her doctor to the mother-to-be, he said. Doctors regularly do similar screening for Rhesus disease.
A triumvirate of leaders
RLYB-211 has gained orphan drug designation from the FDA and the EMA. U.S. gatekeepers have bestowed rare pediatric disease status as well. “We will be working with regulators to see whether we can do a phase II/III registration study once we’ve confirmed the pharmacology and safety,” Uden said.
Martin Mackay, another company founder, said Rallybio’s model dictates hunting outside for molecules and assets. “We do this globally – we have scouts set up in Japan, for example, Israel [and] Europe,” he said. “We cover most of North America ourselves.” The company has a deal with Oxford, U.K.-based Exscientia Ltd., a specialist in artificial intelligence, machine learning and medicinal chemistry.
Also in the Rallybio pipeline is RLYB-212, undergoing preclinical development to address a rare hematologic disease. “We haven’t disclosed the target at the moment, but we are planning to get that into human testing next year and are looking forward to talking more about that when the time is right,” Uden said. Three more preclinical protein therapeutics target rare immuno-inflammatory diseases. A discovery-stage program takes aim at an undisclosed rare metabolic disease.
Jeff Fryer, Rallybio’s third founder, said the series B money will get the pipeline to “value inflection points” and allow for adding more assets. “As we come up to achieving those milestones, we’ll talk about them in a public forum.” Meanwhile, he said, the company is pleased with the quality of investors drawn to the table. “We’re absolutely thrilled and proud to state that the majority of Rallybio employees participated in this financing as well,” he said.
In FNAIT, Mackay said, Rallybio is aware of no competitors, although such might not be the case in other indications pursued. The firm hopes to bring some products to market by itself and collaborate where appropriate. “We’ve all worked for other companies and we know the heavy lift” that self-commercializing entails, he said. “We wouldn’t be averse to doing deals and partnering.”
Mackay said the founders prefer to run Rallybio as a triumvirate of equals. “What is really important in the work that we do is that people know what they’re doing, and they know what they’re accountable for,” he said. “Sometimes, people have so many titles that it’s really difficult to know the job that they do. Legally, we have to do some things that necessitate a title, but that’s not how we work day to day.”
New investors in the series B include Viking Global Investors, TPG’s The Rise Fund, F-Prime Capital, funds managed by Tekla Capital Management LLC, Solasta Ventures, Fairview Capital and Mitsui & Co. Global Investment Inc. Also taking part were existing backers 5am Ventures, Canaan Partners, New Leaf Venture Partners and Connecticut Innovations.