Today it was announced that Rallybio had chosen to discontinue its development of RLYB212 for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT). This is a rare maternal disorder where the mother’s immune system produces antibodies that attack the platelets (thrombocytes) of her baby. This leads to the baby or fetus having a low platelet count, leading to a host of problems.

Things appeared to be going well for this company when it got its phase 2 trial going, but things ended abruptly after today’s announcement. The reason why it chose to end this program using RLYB212 for FNAIT is because of a weak pharmacokinetic [PK] profile. The drug just couldn’t reach the goal of target concentration and that wouldn’t be a good thing going forward. Furthermore, the drug just didn’t meet the minimum concentration necessary to produce any type of adequate efficacy.

This is a huge blow to the company because it could have been a greater than $1 billion market opportunity for it. Not only that, but its pipeline is now reset back to early-stage testing, as the development of the phase 2 study of RLYB212 for FNAIT was the only mid-stage study it had. In essence, it is shifting focus to its C5 inhibitor candidate, known as RLYB116. A confirmatory pharmacokinetic/pharmacodynamic [PK/PD] study using this drug is expected to initiate in Q2 of 2025. This marks a small milestone for investors to keep an eye on.

What’s going to be an even bigger inflection point, though would be the data to be released from this PK/PD study, which is expected to happen in the 2nd half of 2025. It does have some preclinical candidates that are interesting, like REV102 as an ENPP1 inhibitor for the treatment of patients with hypophosphatasia and RLYB332 for the treatment of patients with iron overload.

I would say that the situation for this biotech is dire, as it really needs to achieve a successful outcome with its C5 inhibitor. The good news is that complement inhibition in complement-mediated diseases is a proven model. There are many companies now with approved complement inhibitors. One of the very first C5 inhibitors approved was SOLIRIS [Eculizumab] for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH), which is a rare blood disorder where premature destruction of red blood cells occurs.

With that said, a biomarker analysis done back in December of 2024 showed that RLYB116 was able to achieve greater complement inhibition in a phase 1 multiple ascending dose (MAD) study. It is quite possible that it could go after disorders like PNH, generalized myasthenia gravis (gMG), antiphospholipid syndrome (APS) and complement-mediated disorders. The downside is that it has two uphill battles to climb going forward. One is that it must be able to prove with the release of data in the 2nd half of 2025 that PK/PD data is enough to move forward to the next stage of testing.

Secondly, even if it does somehow eventually get RLYB116 to the finish line, it is going to have to go up against other C5 inhibitors. This means to be worth the effort, it is going to have to beat these other drugs either in terms of safety, dosing regimen convenience, or efficacy. Otherwise, this biotech is going to have a major problem moving forward. It already has an issue in terms of its stock price, where the cutting of the RLYB212 program resulted in the stock price closing the day lower by 41% to $0.25 per share.