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Advancing Pulmonary Arterial Hypertensions (PAH) Therapeutic

Posted on August 15, 2023

Physician-scientists who are awarded a Harrington Scholar-Innovator Award benefit from a two-year term of financial, drug development, project management and business development support. But Harrington’s impact does not end there. Scholars working on promising therapeutics gain access to Harrington Discovery Institute’s mission-aligned partners— through The Harrington Project for Discovery & Development—to ensure that their programs have the greatest potential to advance into the clinic.

The first of such partners is BioMotiv. Harrington Discovery Institute uses its philanthropic funding and drug development expertise to refine a Scholar’s aims and work plan so that the technology progresses to a stage where BioMotiv can help further de-risk the discoveries into medicines that improve the current standard of care for particular diseases.

An excellent example of this model is the work being done by Allinaire Therapeutics LLC (Allinaire) as it pursues a novel biologic approach to treating pulmonary arterial hypertension (PAH). PAH has a three-year mortality rate of greater than 50%, even with the several classes of pulmonary vasodilator treatments, often used in combination, that are the current standard of care.

Irina Petrache, MD, Chief of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, became a Harrington Scholar-Innovator in 2014 when she was at Indiana University for her work on a treatment for chronic obstructive pulmonary disease (COPD) focusing on the pulmonary vasculature.

Working with colleagues at Indiana University, Dr. Petrache provided evidence that a protein in the body, endothelial-monocyte activating polypeptide II (EMAP II), causes inflammation, small airways damage, and apoptosis of the lung endothelial cells—events that are pathological features of COPD. Dr. Petrache and her colleagues, including Matthias Clauss, PhD, patented EMAP II as a target in COPD and formed a company, Emphymab LLC.

As a Harrington scholar, Dr. Petrache’s work was brought to the attention of BioMotiv. Upon learning of Dr. Petrache’s work and Harrington’s support of it, and after extensive due diligence, BioMotiv recommended investment in this exciting discovery in 2016, and obtained an exclusive license from Indiana University. At this time Allinaire was formed by BioMotiv to progress the technology and has worked with Dr. Petrache and her colleagues since then.

Douglas Hay, PhD, working with BioMotiv, was part of the team that performed the due diligence on Emphymab. According to Hay, Dr. Petrache’s Scholar-Innovator grant played an important role in BioMotiv’s decision to invest in the technology.

“We would not have known about the work being done by Dr. Petrache if it hadn’t been for the relationship between Harrington and BioMotiv,” said Hay, who today is Allinaire’s CEO and CSO. “And we probably would not have taken the project directly from the founders, because that would have entailed a much higher risk. So the grant was really key for us, and it led us to a project with outstanding science and researchers, and the possibility of discovering a first-in-class disease-modifying biologic, an anti-EMAP II mAb, for cardiopulmonary diseases.”

BioMotiv’s support continued as the focus of Allinaire’s research shifted from COPD to pulmonary arterial hypertension (PAH). Allinaire is now targeting PAH as the first clinical indication, based upon the strong target validation data, and massive unmet medical need for novel treatments that are non-pulmonary vasodilators, and will slow disease-progression. There is also the potential to expand to other cardiopulmonary diseases, such as COPD and viral-induced acute lung injury, for which there are supportive preclinical data.

“Even though we are still in the preclinical stage, there is a strong level of input and interest from various industry partners, including large pharma,” said Satish Jindal, PhD, CEO of BioMotiv, and Chair, Allinaire. “This is one option among many options to advance the project in the clinic.”

“We discovered that the cytokines that are increased in COPD are also increased in PAH, and that gave us a more specific target that we believe will be easier to push forward with than a heterogeneous disease such as COPD,” Dr. Petrache added. “We have a clear pathway of moving the target forward, and we are grateful to Harrington Discovery Institute and BioMotiv for their support. Without it we wouldn’t have been able to get this far.”

Allinaire has developed about 20 humanized anti-EMAP II mAbs. The next step is lead optimization, and biological and developability characterization of the new mAbs, ultimately leading to the selection of a clinical development candidate. The company hopes to complete that work in late 2023, then move on to manufacturing and safety testing of the selected antibody.

Company Update

Parma, Italy and Cleveland, OH, USA
May 2nd, 2022

Chiesi Farmaceutici S.p.A. (Chiesi Group), the international research-focused pharmaceutical and healthcare group,
announced it has entered into an agreement with Allinaire Therapeutic, LLC, a company founded by BioMotiv, to acquire the world-wide rights to a portfolio of therapeutic monoclonal antibodies (mAbs) against endothelial
monocyte-activating polypeptide II (EMAP II) for the potential treatment of PAH.

Harrington Discovery Institute catalyzed project success with initial grant funding and therapeutic development services to one of the scientific founders, Irina Petrache, MD (Harrington-Scholar Class of 2014) and colleagues at Indiana University and National Jewish Health, together with early seed stage and follow on investments in the company.

About the Scholar

Irina Petrache

Respiratory

Irina Petrache, MD

Indiana University
Harrington Scholar-Innovator

More about Irina Petrache