Scholar Rock Inc.

A differentiated pipeline spanning cancer, fibrosis, and neuromuscular disorders

Although most of Scholar Rock’s drug candidates are in the discovery/preclinical phase, two have shown promising results and are currently undergoing clinical trials.

Apitegromab for Spinal Muscular Atrophy (SMA) – Phase 3 Clinical

Spinal Muscular Atrophy (SMA) is a neuromuscular disorder affecting upwards of 35,000 people in the US and Europe that causes progressive muscle weakness as patients lose motor neurons. This leads to atrophy in the voluntary muscles of the limbs and trunk. SMA is an inherited genetic disorder that usually appears in young children and is often a fatal condition. The cause of SMA has been found to be the insufficient production of a particular protein known as SMN, or “survival of motor neuron.”

SMA patients are characterized as Type 1 through 4, with Type 1 SMA being the most severe and where patients develop disease symptoms even before birth, and Type 4 where patients show symptoms like moderate muscle weakness between 20 and 30 years of age but have a normal life expectancy. 85% of patients are plagued with Type 2 and Type 3 SMA and, therefore, already suffer from significant motor function impairment. Progress has been made in treating SMA by utilizing SMN upregulator therapies, which address SMN deficiencies by preventing further motor deterioration.

In order to address the unmet need for effective therapies that go beyond prevention and actually improve functional performance, Scholar Rock is developing Apitegromab. This muscle-directed therapy can be used in conjunction with SMN upregulator therapy to more comprehensively treat SMA. Apitegromab is an inhibitor of latent myostatin, a protein secreted in muscle tissues that inhibits muscles from growing abnormally large. In SMA patients, muscle atrophy is caused by the loss of motor neurons that results in weak signaling between the skeletal muscle and nerve, not by any abnormalities in the skeletal muscle itself. By inhibiting myostatin, Apitegromab aims to improve SMA symptoms by allowing an environment where fast-twitch muscle fibers remain present and could potentially form but aren’t deteriorating without use.

SRK-181 to treat cancers that are resistant to checkpoint inhibitor (CPI) therapies – Phase 1 Clinical

An estimated 750,000 cancer patients in the US each year are eligible for treatment through checkpoint inhibitor therapies, particularly anti-PD-1 or anti-PD-L1 antibody therapies. Checkpoint inhibitor therapies target immune checkpoint proteins whose occurrence within a tumor inhibits the immune system’s response and allows the tumor to evade being killed. However, the majority don’t respond well to treatment because they have pre-existing or primary resistance to immunotherapy.

Scholar Rock’s SRK-181 is a selective inhibitor of the latent transforming growth factor beta-1. With this drug candidate, Scholar Rock is aiming to treat cancers that are resistant to anti-PD-(L)1 antibody therapies. When implementing a combination treatment plan of SRK-181 and an anti- PD-1 antibody in mouse modules, this combination showed promising results, as tumor regressions were quite substantial. This combination is going through ongoing human testing in Phase 1 clinal trials.

Operational overview

Scholar Rock outsources all of its clinical drug manufacturing needs to third-party manufacturers. The company has yet to have any product candidates make it successfully through clinical trials and therefore has generated no revenue from approved drugs. Scholar Rock has previously generated revenue through two now terminated licensing agreements with Janssen Biotech and Gilead Sciences but does not currently have any committed external sources of funding.

The company has primarily financed operations through equity financing like common stock, collaboration agreements, and a loan from its debt facility. Unless the company can attract viable partners to enter into further revenue-generating collaboration agreements, it’s likely Scholar Rock will need to generate additional funding through further equity offerings and debt financing. The company has already issued numerous warrants and equity awards that are exercisable into common stock, which could result in a substantial dilution of ownership for current stockholders.

Conclusion

Scholar Rock’s alternative approach to tackling rare diseases is based on a longstanding biological fact that protein growth factors play a significant role in cell regulation. Even though growth factor therapies have shown promise and scientific backing, targeting active growth factors has repeatedly led to unintended negative consequences on the body as these therapies have not been able to selectively target the intended growth factors. However, by taking the unexplored route of targeting latent growth factors instead of active ones, Scholar Rock could be on the cusp of finally overcoming the selective targeting pitfalls of previous attempts and producing effective growth factor-based therapies for applications across a multitude of rare diseases.