Serpin Pharma is a privately held biotech company with research facilities in Northern Virginia, USA. Serpin’s dedicated and experienced management team is committed to commercializing first-in-class, anti-inflammatory, and immune-modulatory peptides for treatment of inflammatory, autoimmune, and infectious diseases.

AAT – $700M in sales, potential >>$4B

Alpha-1 antitrypsin (AAT) is the best characterized human Serpin and the second-most abundant plasma protein. AAT is an acute-phase protein whose level increases during inflammation. Its function is to block serine proteases, reducing tissue damage, and to induce production of anti-inflammatory mediators.

There are currently three FDA-approved AAT products on the market for treatment of AAT deficiency (Prolastin, Zemaira and Aralast). All are purified from human plasma and face manufacturing, supply, and cost challenges. Nevertheless, their combined annual sales amount to approximately $700M, with an estimated market potential exceeding $1.2B. Ongoing clinical trials are designed to expand the use of AAT to treatment of new-onset type I diabetes, cystic fibrosis, and graft-versus-host disease, thereby increasing the combined market potential to several billion dollars annually.

Serpin Pharma’s lead drug candidate

SP16, Serpin Pharma’s lead product, is a first-in-class peptide drug derived from AAT. An extensive pre-clinical data package shows SP16 comprises AAT’s anti-inflammatory and immune-modulatory properties, making this readily available peptide a bio-superior to AAT in a range of inflammatory and autoimmune diseases. SP16 targets critical immunological pathways and is predicted to become a paradigm-shift therapeutic for treatment of autoimmune disease, devoid of the non-specific, detrimental immune suppression side effects caused by other drugs.

SP16 is positioned as a Bio-superior anti-inflammatory drug derived from the marketed AAT drug. Its key advantages over AAT include increased potency, ease of manufacturing, availability, cost, strong and unique IP, and extraordinary benefit to patients and payers.


The lead indication for SP16 development is Acute Myocardial Infarction (AMI), which represents a multi-billion-dollar market. (The cardiovascular market is estimated at $110B in healthcare costs). The inflammatory response as a result of tissue injury is necessary for the clearance of cellular debris [1,2]. Low-density lipoprotein receptor related protein-1 (LRP1) is a ubiquitous membrane receptor functioning as a scavenger and regulatory receptor [3-5]. Its expression increases during hypoxia, ischemia, and tissue injury [3-6]. LRP1 is a non-selective receptor, binding several plasma proteins [3-6]. Also known as alpha-2 macroglobulin (A2MG) receptor, LRP1 has the ability to bind the complex of A2MG and plasma proteases [7-8]. The binding of the protease/inhibitor complex to LRP1 is seen across the entire spectrum of serine protease inhibitors (SERPINs) such as alpha-1 antitrypsin (AAT) and antithrombin III (ATIII), and is referred to as SERPIN-enzyme complex (SEC) receptor [3-5] The binding of protease/inhibitor complexes to LRP1 inhibits the inflammatory response [5] and induces a pro-survival signal through phosphorylation of protein kinase Akt [9]. In preclinical animal studies, the administration of plasma-derived AAT or ATIII led to a significant reduction in myocardial injury in experimental acute myocardial infarction (AMI) [10-11]. We therefore hypothesize that the synthesis of an LRP1 agonist in the form of a small peptide would provide cardio-protection in AMI.

Reperfusion strategies have been successful in shortening the duration of ischemia, thus reducing infarct size. Prevention of mitochondria-mediated events have only partially and inconsistently translated into reduction in infarct size in preclinical and clinical studies, possibly because treatment is effective only if administered prior to ischemia or reperfusion [31], limiting the clinical applicability of these strategies due to their narrow therapeutic window. There are no clinically available strategies to limit the inflammatory injury [22,31]. Treatment with SP16 may therefore represent a significant step forward in the treatment of AMI by providing an effective strategy limiting inflammatory injury following reperfusion. SP16 also provides several clear advantages over the use of plasma-derived formulations of SERPINs. SP16 contains the SERPIN’s highly-conserved motif required for LRP1 binding and shown to exert an anti-inflammatory action, devoid of any inhibition of plasma proteases.

Unlike SERPINs, SP16 is already active and does not require interaction with serine proteases to become active. SP16 does not require isolation from the plasma, limiting the inherent infectious and/or anaphylaxis risks. On the other hand, being highly homologous to the C-terminus of SERPINs, SP16 is expected to have a very high tolerability and safety profile, as shown in the preliminary toxicology profile. In patients with ST-segment elevation AMI, plasma-derived AAT was safe and associated with a blunted inflammatory response [32]. Moreover, the synthesis of SP16 is rather inexpensive and is not affected by potential limitations in plasma supply. Given the smaller molecular weight and efficacy at low doses, SP16 can be given subcutaneously, thus facilitating administration.


In conclusion, LRP1 activation with SP16 during experimental AMI leads to a cardio-protective signal that reduces infarct size and preserves cardiac systolic function in mice. SP16 represents a first-in-class pharmacologic agent for exploring an entirely novel approach of cardio-protection in AMI.

Concurrently, Serpin Pharma is exploring strategic opportunities for the joint development of two additional IP-protected serpin peptides – SP9 and SP14 – as treatment for cystic fibrosis and septic shock in burn patients.


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Research and Development

Serpin Pharma has developed a family of synthetic peptides derived from naturally occurring serine protease inhibitors (Serpins) containing a unique anti-inflammatory core motif. These peptides retain the anti-inflammatory and cell-protective signaling without inhibiting the plasma serine proteases.

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