RLYB - Rallybio: Early Stage Developer With Proof Of Concept Data

2023-03-15 07:29:49 ET

Summary

• RLYB has a diverse pipeline targeting rare diseases.
• Recently, it announced proof of concept data.
• The company has a decent cash runway and looks interesting.

Rallybio ( RLYB ) is a microcap, early stage developer of rare disease therapeutics. The company’s science is all over the board, with monoclonal antibodies, small molecules, pegylation, and so on. The pipeline is here:

Lead asset RLYB212 is an Anti-HPA-1a Monoclonal Antibody targeting FNAIT or Fetal and neonatal alloimmune thrombocytopenia. This disease affects newborns, and usually presents as thrombocytopenia that is very severe in otherwise healthy babies. The disease is rare, with a prevalence of 1 to 5 in 10,000 live births. The US had 3.6 million live births in 2021. Thus there should be between 365 and 2000 American patients, a similar number in Europe, and so on.

About the etiology and treatment of FNAT, orpha.net notes :

Etiology

FNAIT results from the transplacental passage of maternal alloantibodies (which are IgG) against fetal platelet antigens which are inherited from the father. In Caucasians, the most frequent platelet antigen (HPA) involved in FNAIT is HPA-1a (anti-HPA-1a alloantibodies), which is located on glycoprotein IIIa (GPIIIa), accounting for 75-80% of cases. The other main antigens involved are HPA-2, HPA-3, HPA-5, and HPA-15. The mechanisms of maternal immunization are only partly understood. Fetal syncytiotrophoblasts express GPIIIa on their cell surface and the spread of their extracellular vesicles in the maternal circulating blood system may possibly be at the origin of immunization, beginning with the first pregnancy.

Management and treatment

Post-natal management involves transfusion of platelets devoid of this antigen, and should not be delayed by biological confirmation of the diagnosis (once the diagnosis is suspected), especially in case of severe thrombocytopenia. Prompt diagnosis and treatment are essential to reduce the chances of death and disability due to hemorrhage. Due to the high rate of recurrence and increased severity of the fetal thrombocytopenia in successive pregnancies, antenatal therapy should be offered. Fetal blood sampling by cordocentesis remains possible in situations of intermediate risk if there is a question about the indication of medical treatment and where vaginal delivery is requested.

HPA-1a is the most common antigen involved in Caucasians, and RLYB212 targets this antigen, potentially preventing alloimmunisation, where the mother’s immune system attacks the fetal platelets. There is no approved treatment and the only option is platelet transfusion, however, the disease can quickly lead to intracraneal haemorrhage, and lifelong neurological problems. However, at-risk pregnancies can be easily diagnosed for HPA-1a negative patients through standard prenatal screening. The molecule is delivered subcutaneously no more than once a week. RLYB212 is covered by composition of matter patents. It has orphan designation from the US and EU and rare pediatric disease designation in the US.

In preclinical trials, the molecule has shown signs of efficacy. A presentation titled “Rapid and Complete Clearance of HPA-1a Mismatched Platelets in a Human Model of Fetal and Neonatal Alloimmune Thrombocytopenia by a Hyperimmune Plasma Derived Polyclonal Anti-HPA-1a Antibody” was published in 2021. Data showed :

RLYB211 1000 IU provides proof of concept of the ability of anti-HPA-1a antibodies to rapidly and completely clear mismatched HPA-1a/b positive platelets in HPA-1b/b individuals. RLYB211 1000 IU was safe and well tolerated and no SAEs were reported.

RLYB211 has now been shelved for a more updated version, 212.

An article in the Blood Journal also presents more preclinical data :

In the current study, Zhi et al report a preclinical investigation of the ability of human HPA-1a antibodies to prophylactically prevent maternal alloimmunization and development of FNAIT. They used their recently established alloantigenspecific FNAIT mouse model, which preimmunizes wild-type female mice with platelets from transgenic mice expressing the human HPA-1a epitope on a murine glycoprotein IIIa backbone (termed APLDQ GPIIIa). This results in the generation of HPA-1a alloantibodies that can recapitulate FNAIT clinically when these female mice are bred with HPA-1a–positive male mice. Using this elegant alloantigen-specific FNAIT mouse model, two human HPA-1a–specific antibodies were preclinically evaluated: RLYB211 (polyclonal antibody) and RLYB212 (monoclonal antibody). It was observed that both antibodies could effectively clear HPA-1a–positive murine platelets from the circulation and prevent the occurrence of alloimmunization (determined by the presence of antibodies reactive against APLDQ platelets).

Thus, there’s considerable preclinical data that shows that RLYB212 is effective as a prophylactic treatment of FNAIT.

Just last week, the company announced that its phase 1b trial has achieved proof of concept and that a single subcutaneous dose of RLYB212 was able to eliminate transfused, HPA-1a positive platelets in HPA-1a negative subjects within one week after dosing. A registrational study will be done after this.

Second asset is C5 inhibitor RLYB116. A single ascending dose phase 1 trial is ongoing (not seen on the registry because it is partnered with original developer Affibody). PK/PD data is here . Other assets are in preclinical stages.

Financials

RLYB has a market cap of $200mn and a cash balance of $169mn. R&D expenses were $10.8 million for the fourth quarter of 2022, while G&A expenses were $6.3 million. That gives the company a 10 quarter runway at this rate.

Rallybio management consists of a number of ex-Alexion execs. The company has a partnership deal with AbCellera, a much larger company, for a few of their preclinical assets.

Bottomline

Rallybio seems like an interesting company with a diverse pipeline and proof of concept data for its lead asset. I will watch RLYB stock for a speculative entry point.

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