Rescuing Uncontrolled Bleeding with Haima Therapeutics

The challenges of uncontrolled bleeding

Blood plays a vital role in transporting oxygen and nutrients to cells throughout the body, as well as removing waste products. When a blood vessel is damaged, whether by traumatic injury, surgery, or disease, it may rupture, leading to bleeding. Uncontrolled bleeding is characterized by excessive and uncontrollable loss of blood from the circulatory system. Regardless of its origin, uncontrolled bleeding poses a significant risk to health and can lead to severe complications, including acidosis (too much acid in the body), hypothermia, and organ failure.  Trauma-induced bleeding specifically is the leading cause of death in Americans aged between one and fifty years old.

There are several types of uncontrolled bleeding, each with its own mechanisms and implications for health:

• Traumatic Bleeding: This type of bleeding occurs as a result of physical injury, such as cuts, lacerations, puncture wounds, or blunt force trauma. Traumatic bleeding can range from minor abrasions to severe, life-threatening injuries, depending on the extent of tissue damage and the location of the injury.
• Surgical Bleeding: During surgical procedures, incisions are made into tissues, which inevitably involves cutting blood vessels. While surgeons take precautions to minimize bleeding through techniques such as cautery and suturing, surgical bleeding can still occur, especially in complex or invasive procedures.
• Spontaneous Bleeding: Some medical conditions can predispose individuals to spontaneous bleeding due to abnormalities in the blood vessels or clotting factors. Hemophilia, von Willebrand disease, and thrombocytopenia (low platelet count) are examples of disorders that can result in spontaneous bleeding episodes without external trauma.
• Bleeding due to anti-platelet or anti-coagulant therapy: Medications such as anti-platelet agents (e.g., aspirin, clopidogrel) and anti-coagulants (e.g., warfarin, heparin, direct oral anticoagulants) are prescribed to prevent thrombotic events in individuals at risk of conditions like stroke, myocardial infarction, and deep vein thrombosis. However, these medications can impair the hemostatic process, increasing the risk of bleeding. Anti-platelet drugs inhibit platelet aggregation, reducing the formation of the initial platelet plug, while anti-coagulants interfere with the coagulation cascade, preventing the stabilization of blood clots. As a result, patients on these therapies are at heightened risk for both minor and major bleeding episodes, including spontaneous bleeding and excessive bleeding from minor injuries or surgical procedures.

Bleeding can be categorized by the site at which bleeding occurs. Examples include gastrointestinal bleeding (which can be due to  to ulcers, inflammation, tumors, or vascular abnormalities within the digestive system), menorrhagia (heavy menstrual bleeding), postpartum bleeding (bleeding after giving birth), epistaxis (nose bleeds), hemorrhagic stroke (bleeding into the brain, which accounts for 13% of all strokes), hemarthrosis (bleeding into the knee, a common feature of hemophilia), and so on.

Non-compressible uncontrolled bleeding presents a particularly challenging scenario in medical practice. Unlike bleeding from superficial wounds that can often be managed by direct pressure, non-compressible bleeding occurs from deep-seated sources within the body, making it difficult to control using traditional methods. Common examples of non-compressible bleeding include injuries to vital organs or major blood vessels. These injuries may occur as a result of trauma, such as vehicular accidents, falls from height, or penetrating injuries from sharp objects or bullets (such as in military settings). Non-compressible uncontrolled bleeding carries a high mortality rate, particularly in the context of trauma or severe medical conditions. Without timely access to advanced medical care and interventions such as surgery, blood and platelet transfusions, and resuscitative measures, outcomes can be grim.

The Body’s Natural Response to Bleeding

The process by which our bodies naturally stop bleeding following injury is called hemostasis. Hemostasis involves a complex interplay of cellular and molecular components, including platelets, blood vessels, and coagulation factors, to form a stable blood clot at the site of injury. In the first step of hemostasis, called the Vascular Phase, vasoconstriction occurs to reduce blood flow and limit the loss of blood. Following the Vascular Phase is the Platelet Phase, during which platelets adhere to the exposed cell matrix of the damaged blood vessel walls. This process is facilitated by the von Willebrand factor (vWF), which acts as a bridge between platelets and collagen fibers in the injured tissue. Once adhered, platelets become activated, changing shape, expressing cell-surface receptors and releasing various molecules, such as adenosine diphosphate (ADP) and thromboxane A2 (TXA2), which recruit and activate additional platelets, amplifying the hemostatic response. This leads to the formation of a platelet plug, which temporarily seals the breach in the vessel wall. In the Coagulation Phase, clotting factors in plasma are activated, which results in the integration of a fibrin mesh with various blood cells and the platelet plug to form a clot.

Platelets are cells without a nucleus that circulate in the blood and touch every organ system in the body; they are considered nature’s drug delivery vehicles. The proper functioning of platelets is essential for effective primary hemostasis. Platelet disorders, such as thrombocytopenia (low platelet count) or platelet function defects, can impair the formation of a platelet plug, leading to prolonged bleeding times and increased susceptibility to bleeding. Conversely, elevated platelet function can increase the risk of inappropriate platelet activation, which can cause thrombosis and, consequently, myocardial infarction, pulmonary embolism, venous thromboembolism or ischemic stroke. Beyond hemostasis, platelets also play a role in other physiological mechanisms and pathological conditions in the body, such as cancer metastasis, neurodegeneration, and inflammation. 

In the context of non-compressible uncontrolled bleeding, platelets play a vital role in slowing down bleeding by contributing to the formation of a stable blood clot. The transfusion of platelets from blood donors demonstrably lowers the mortality rate of patients with uncontrolled bleeding, when the transfusion occurs early enough. The standard of care for surgery patients and trauma patients who are rapidly losing large volumes of blood, named massive transfusion protocol, depends on the rapid delivery of a 1:1:1 mix of platelets, red blood cells, and plasma. However, hospitals encounter several challenges in maintaining platelets for emergency patient use:

• Availability: Platelets, like red blood cells and plasma, are dependent on donors. Availability is low in both civilian and military settings, with over 50% of the US population living over an hour away from a  trauma center.
• Blood-type matching: To prevent immunogenic response, blood products must be matched to patients based on ABO blood type and Rh factor. In addition, platelet transfusion refractoriness (patients who respond suboptimally to platelet transfusions)  requires the special provision of matched platelet sourced from a small pool of genotyped donors.
• Storage: Platelets must be preserved under specific environmental conditions, which brings up additional challenges in portability, so that they may be accessed outside of trauma hospital settings.
• Shelf-life: Platelets carry a risk of bacterial contamination, and are only stored for up to 5 days if unused. Up to 20% of platelets are discarded due to this short shelf-life.

Haima’s Technology

In response to these challenges, Haima Therapeutics developed their lead product, Synthoplate. Synthoplate is a platelet-inspired synthetic cell therapy that mimics some of the mechanisms that platelets use to control bleeding. Synthoplate consists of synthetic nanoparticles that mimic and combine several of platelets’ hemostatic mechanisms. The Synthoplate nanoparticles are coated with thousands of copies of the same peptides that allow natural platelets to bind at the injury site, and can bind to other activated platelets, leading to the platelet aggregation effects necessary to form a stable clot.

Importantly, unlike platelet transfusions from blood donors, Synthoplate particles are fully synthetic and can be manufactured at a large scale, they have a long shelf life and can be stored in space-saving formats for easy portability and pre-hospital availability. Synthoplate can be administered through IV infusions, and because the particles do not express potentially immunogenic antigens, do not require blood-type matching.

Spinal surgery is Haima’s first chosen indication. Nearly 500,000 spinal fusion surgeries are performed per year in the US alone, with up to 80% experiencing excessive bleeding that requires hemostatic intervention and/or transfusion. These are one of the most common open surgeries with a medium-to-high risk of uncontrolled bleeding.

Haima’s Story

Haima Therapeutics was co-founded by Drs. Anirban Sen Gupta and Christa Pawlowski in 2016, emerging from pioneering research at Case Western Reserve University (CWRU). Since its inception, Haima’s research and development efforts have been robustly supported by more than $14 million in federal grants.

Dr. Sen Gupta, a full-time professor at CWRU, began working on synthetic platelets in 2009, which marked the nascent stage of what would become SynthoPlate. Christa Pawlowski joined his lab as an undergraduate researcher around the same time and was instrumental in advancing this project. She continued her work as a graduate student under Dr. Sen Gupta, earning her PhD in 2015 with an impressive portfolio of 17 peer-reviewed publications. During her postdoctoral tenure in Dr. Sen Gupta’s lab, Christa secured early-stage funding through multiple avenues. These accomplishments provided a solid foundation for starting Haima Therapeutics in 2016. Haima’s journey in securing significant external funding began with a Phase 1 SBIR grant from the NSF in early 2018, coinciding with Haima’s CEO Dr. Michael Bruckman joining the company. This milestone marked a new chapter in Haima’s pursuit of advancing synthetic platelet technologies. 

Haima Therapeutics is a stellar addition to Tachyon’s portfolio, epitomizing our commitment to investing in companies that develop groundbreaking mechanistic solutions with broad medical applications. We are excited about Haima's platelet-inspired technology and its potential to not only address bleeding but also hold promise for treating a range of blood disorders, including thrombosis, inflammation, and cancer. Supporting Haima in its journey aligns seamlessly with our vision of fostering advancements that can revolutionize healthcare.