The American Society of Hematology (ASH) held its 64th Annual Meeting from December 10-13, 2022. During the meeting, doctors, researchers, and other stakeholders within the hematology sphere came together to discuss best clinical practices, treatments and trends, and new research findings.

One of the presentations shared came from AltruBio, a privately held biotechnology company that is focused on developing novel therapeutics for immunological diseases with high unmet needs. Within the presentation, entitled “Neihulizumab (ALTB-168) in Patients with Steroid-Refractory Acute Graft-Versus-Host Disease (SR-aGVHD) or Treatment-Refractory Acute Graft-Versus-Host Disease (TR-aGVHD),” Dr. Sameem Abedin, MD, a principal trial investigator, shared data from a completed Phase 1b study.

As the presentation name suggests, the study explored neihulizumab (ALTB-168) for patients with different forms of graft-versus-host disease (GvHD). If you are interested in looking at Abstract #163027, you may do so on the ASH Annual Meeting website.

Recently, Patient Worthy sat down with Dr. Jesse Hall, M.D., the Chief Medical Officer of AltruBio. In our discussion, we talked about what ALTB-168 is, why the findings presented at the ASH Annual Meeting are so meaningful, and the rewards and challenges of drug development.

About Dr. Jesse Hall, MD

Dr. Jesse Hall earned his BA in Ocean Studies with a minor in Economics from the University of San Diego, and later went on to earn his MD from the University of Oklahoma College of Medicine. He shares:

“I’m a physician by training, but transitioned into the pharma and biotech industry, which is where I’ve been for the last twenty years or so. I began my career in medical affairs at Abbott Laboratories working in immunology. After spending time there, I knew that I wanted to move into the development space. So I became a Medical Director at Amgen in the rheumatology space, where I was able to work on early development programs such as a registrational program for male osteoporosis.”

Wanting to expand his career into the early development space, Dr. Hall then moved to San Diego to work as Executive Medical Director of Ardea Biosciences.

Prior to joining AltruBio as the company’s CMO, Dr. Hall served as CMO and Executive Vice President at Sublimity Therapeutics. What eventually brought him to AltruBio, he explains, was that:

“The management team and board were very well-experienced, and I was fascinated by the novel approach to immunology. Targeting late-stage, chronically activated T-cells rather than blocking an acute inflammatory response made sense to me. I was excited by AltruBio’s science and the potential of advancing it for patients.”

Graft-versus-Host Disease (GvHD): A Brief Overview

Graft-versus-host disease (GvHD) is a rare and potentially serious complication which can occur after an allogeneic transplant of either stem cells or bone marrow. This condition results from transplanted cells that view the recipient’s body as foreign. These cells then attack the recipient’s body, causing a variety of health effects. GvHD may be acute (occurring within six months after transplant) or chronic (occurring more than three months following a transplant with symptoms that last long-term).

Symptoms differ between the two subtypes. In acute GvHD, symptoms can (but do not always) include:

• Nausea and vomiting
• Jaundice (yellowing of the skin, eyes, and mucous membranes)
• Diarrhea
• Skin rash, redness, or itchiness
• Abdominal pain or cramping
• Increased risk of infections

Symptoms related to chronic GvHD can include:

• Unintended weight loss
• Joint pain or stiffness
• Fatigue
• Muscle weakness
• Dry eyes and/or mouth
• Pain or sensitivity to spicy food
• Changes in vision
• Shortness of breath or a dry cough
• Difficulty swallowing

Treatment Options

Currently, there are a few therapeutic options for those with GvHD. Patients usually take immunosuppressants following the transplant to reduce the risk of GvHD. For those with the chronic form, prednisone and immunosuppressants may be helpful. But, Dr. Hall explains, these treatments have been seemingly unable to return immune cells to a lower state of activation:

“Current standards-of-care often focus on blocking the initiation of the immune response or are more broadly immunosuppressive. We developed ALTB-168 as a more targeted treatment option. The unique component of our mechanism is that it only binds to those late-stage active T cells that you want to eliminate: those that have not been able to self-regulate to a state of quiescence, which is the normal homeostatic state that you want to see in the immune system. We’re able to push them towards this natural resolution.”

Developing Neihulizumab (ALTB-168)

Dr. Hall has played a role in the company’s development of ALTB-168, which is being developed for a series of indications. Outside of GvHD, AltruBio is currently exploring ALTB-168 as a potential treatment option for patients with active psoriatic arthritis and ulcerative colitis.

AltruBio describes ALTB-168 as:

“A humanized therapeutic antibody with a unique mechanism of action, preferentially inducing apoptosis (cell death) of late-stage activated T cells. This novel activated T-cell apoptosis-inducing antibody effectively eliminates chronic pathogenic T cells while fully maintaining host defense, leading to durable clinical efficacy without increasing the risk of infection or cancer.”

Dr. Hall builds upon this explanation, explaining:

“Traditionally, PSGL-1 is a cell surface protein that is expressed on cells of the immune system. It was thought to be involved in the trafficking of these cells to sites of inflammation and allowing these cells to get into tissues where inflammatory signals have been perceived. Our team was the first to describe the role PSGL-1 plays in up- and down-regulating immune cells. So ALTB-168 acts as a PSGL-1 agonist. By binding to a certain portion of this protein, you see a downregulation of immune cells and are able to effectively resolve inflammation. It works for diseases with a high preponderance of active, chronically late-stage T-cells that haven’t returned to acquiescence.”

Of course, the drug development process can be challenging. One of the most challenging parts, Dr. Hall explains, is raising the finances to fund and advance these programs. But at the end of the day, the science – and the ability to bring therapies to patients in need – is worth it.

Studying ALTB-168

So far, studies of ALTB-168 have shown that the treatment is effective in reducing disease activity in indications such as ulcerative colitis, psoriatic arthritis, and psoriasis. The challenge of progressing ALTB-168 was accessibility and administration. ALTB-168 is administered via IV infusion and, to maximize the efficacy, must be given weekly. Since patients with GvHD are frequently seen by physicians and closer to treatment centers for IV infusions, moving ALTB-168 to this indication seemed like a natural progression.

At the ASH Annual Meeting, AltruBio shared data from a Phase 1b clinical study evaluating ALTB-168 for patients with steroid-refractory or treatment-refractory GvHD. This means that patients have failed corticosteroids and other standards-of-care; these patients have a significant unmet medical need. Given that up to 60% of patients become refractory to corticosteroids, a novel, safe, and effective therapeutic option is urgently needed.

Unpacking the Findings

Altogether, 24 patients enrolled in the trial. 50% were steroid-refractory and 50% were treatment-refractory. Patients were treated and evaluated over a 28-day period. Findings from the study include:

• Patients with steroid-refractory GvHD achieved an overall response rate (ORR) of 67% and a complete response (CR) rate of 17%.
• Those with treatment-refractory GvHD achieved an ORR of 67% and a CR of 25%.
• ALTB-168 was safe and well-tolerated, both when used alone or when used in conjunction with other therapies.
• After 180 days, 11 patients (five with steroid-refractory GvHD and six with treatment-refractory GvHD) were still alive.

Says Dr. Hall:

“We saw the greatest effects in the treatment-refractory patients. An ORR of 67% is pretty remarkable when you compare it to the historical response rates, which are closer to 35%. The most encouraging data, and what we were most excited to see, was that median survival increased significantly. Some recent studies on treatment-refractory disease show that patients have a 21-28 day survival range. In our patients, median survival exceeded 180 days. Most patients will die without appropriate therapy and we are really hoping that ALTB-168 will address that need. And by presenting at ASH, we’re not only showing the promise of this therapy but potentially finding a partner to help us navigate through the clinical development stages.”

Next Steps

Moving forward, Dr. Hall hopes that AltruBio will be able to have regulatory interactions with the FDA to begin finding a regulatory path forward for ALTB-168.

Outside of this therapy, the company is also working on a next-gen therapy which binds to the epitope of the PSGL-1 molecule: ALTB-268. This potent therapy allows for subcutaneous dosing, making it a more patient-focused approach. AltruBio recently had its Investigational New Drug (IND) application approved for ALTB-268 and will be initiating a first-in-human trial within the next year.