PharmaShots Interview: Paracrine's Christopher J. Calhoun Shares Insight on the First Autologous, Device-Based Cell Therapy Platform

In an interview with PharmaShots, Christopher J. Calhoun, President & CEO at Paracrine shared his views on the transforming diabetes treatment with the first autologous, device-based cell therapy platform

Shots:

The company has developed the first autologous, device-based cell therapy platform which is ideally positioned to address conditions with underlying integers
Paracrine is a one-time, completely natural procedure that works through interactive 'Paracrine signaling' & is the safest and most cost-effective cell therapy for the patients
Paracrine procedure is a 3-step process & it takes about an hour' In 1st step, a small amount of fat is removed from the belly or thighs of a patient & then processed in the Celution System via a single use consumable in 2nd step after that patient's own stem and regenerative cells are ready to be delivered back into the patient in the 3rd step

Tuba: Introduction to Paracrine, the cell therapy platform, and what has been accomplished to date

Christopher J. Calhoun: Paracrine is a biopharmaceutical company that is currently developing the world's first device-based, autologous cell therapy platform that is focused on late-stage clinical trials for some of the greatest unmet needs in healthcare today.

With 20 years of development and upwards of $400 million invested into this technology, the design, engineering, and manufacturing of the Celution System, as well as the basic science, pre-clinical studies, and extensive clinical development work have all been completed. This positions us to entirely focus on executing pivotal (e.g., approval) trials to rapidly get this to market and the patients in need.

An estimated 8,000 to 10,000 people have already been treated with Paracrine's Celution System worldwide, including 80 investigator-led studies and 9 sponsored clinical trials.

This not only provides tremendous confidence that the therapy is safe but it provides valuable insight into how it's working; what indications it's working in, and most importantly, where it may not yet be working.

Building on this knowledge and all our clinical experience, we are now advancing three late-stage trials with a high probability of success.

Tuba: What is the Paracrine procedure?

Christopher J. Calhoun: This is an easy 3-step process.

First, a small amount of fat' half a can of coke worth, is removed from the belly or thighs of a patient.

Second, it is then processed in the Celution System via a single-use consumable.

Third, the patient's rich population of stem and regenerative cells are ready to be delivered back to the patient.

The entire process takes about an hour.

Tuba: Why Fat?

Christopher J. Calhoun: Adipose Tissue (fat) is well known as the body's 'energy storage' department. Recently, the role and importance of adipose tissue have been expanded and adipose tissue is now recognized as the body's largest endocrine organ, secreting more than 600 different proteins, hormones, peptides, and cytokines - called 'Adipokines'.

Adipokines are essentially chemical messages or instructions' that is, a way for cells to communicate with each other. We call this the Language of Healing. These molecules participate through paracrine and endocrine 'cross-talk' in a great variety of physiological processes, thereby regulating numerous biological functions including the immune system, inflammation, and vascular function (among many others).

Whereas endocrine communications are generally thought of as long-distance calls' typically using the vascular system to transport messages' Paracrine signals are short-distance communications typically between cells that are local. ADRCs likely employ both endocrine and paracrine signaling, with an emphasis on paracrine or local, messaging and cross-talk.

Furthermore, adipose has also recently been described as the body's most active immune organ. Adipose Tissue contains all types of immune cells including approximately 30% of the body's regulatory T-Cells (Tregs). Approximately a quarter of the ADRCs in Paracrine Cell Therapy are macrophages.

Macrophages are best known for a classical pro-inflammatory phenotype and secretion of Interleukin-6 (IL-6), which has a reputation as one of the more notorious pro-inflammatory cytokines. But, macrophages have the unique ability to flip or 'polarize' into an opposing M2 phenotype. So, the M2 macrophage secretes immunosuppressive factors and anti-inflammatory cytokines such as IL-10 and IL-1Ra result in a reduction of IL-6. The majority of macrophages in adipose tissue are M2 phenotype and are likely responsible for the beneficial anti-inflammatory and immunosuppressive effects we have documented in clinical and pre-clinical studies with ADRCs.

Therefore, ADRC's amplify the body's innate ability to heal itself through dynamic signaling (cross-talk) that reduces inflammation, suppresses the immune system, improves local blood flow & vascular structures, and repairs damaged tissue.

This is the world's first 3-in-1 cell therapy: Vascular Therapy, Immunotherapy, and Regenerative Therapy.

Tuba: What is cell therapy's role in treating diabetes-related complications?

Christopher J. Calhoun: The common pathology behind many diabetes complications starts with endothelial dysfunction, which leads to micro and macrovascular damage and more specifically , local tissue ischemia (or impaired blood flow), global and localized inflammation, and subsequently, tissue damage. This creates a negative spiral of progressive disease which worsens over time. This can also be accelerated by an event such as a stroke or a heart attack which triggers the spiral of progressive disease.

Paracrine Cell Therapy is ideally positioned to address conditions with these common underlying integers. Unlike most drug therapy which typically targets a single mechanism of action and focus on symptoms (block the pain receptor and your headache goes away for a while), our cells respond dynamically to the local environmental cues, addressing each of the core structural issues.

Initially, the cells respond to the local ischemia by releasing various pro-angiogenic factors that repair or rebuild necessary vascular structures to improve the local blood flow. Then they begin to suppress the local immune system and down-regulate inflammation that is, switching from pro-inflammatory to anti-inflammatory positioning. Finally, they recruit and direct the rebuilding and remodeling of tissue that has been damaged. This restores function and may alleviate chronic symptoms like pain or heal otherwise non-healing wounds.

Complex conditions such as these require dynamic (biologic) multi-modality therapy. In other words, a silver bullet just isn't going to work. By addressing the underlying structural issues, Paracrine effectively changes the pathophysiology, breaking the spiral of progressive disease.

Tuba: What are Paracrine's future plans?

Christopher J. Calhoun: My number one job is to get the clinical data needed by the FDA to gain approval as quickly as possible, to bring this important technology to many patients who need advanced therapy. We are focusing and resourcing the company exclusively around this core mission.

What's different about Paracrine is the overwhelming amount of clinical data and experience that we already possess. This makes my job easier since we can select multiple indications with the highest probability of success and in parallel, significantly mitigate any clinical risks.

Keep in mind this does not mean targeting low-risk or inconsequential indications. We are targeting one of the leading causes of death in the ATHENA III Heart Failure Trial; the leading cause of hospitalizations of diabetics in the ASCEND Non-Healing Diabetic Foot Ulcer Trial, and the STAR II Trial we are currently treating the debilitating hand dysfunction due to scleroderma, a rare autoimmune rheumatic disorder that has confounded scientists for decades.

For each trial, we are working with the topmost clinical specialists in the field, a fact of which I am very proud.

Each of these indications shares a common underlying pathology including ischemia (impaired blood flow), inflammation, and tissue damage making them ideal targets for Paracrine's '3-in-1' therapy.

One more interesting point is in all of these trials, and more broadly in nearly all of the patients treated to date globally, is that this is a 'one and done' therapy. Meaning, the patient needs only to be treated one time.

Tuba: What makes Paracrine so cost-effective on the business end, and affordable for the patient?

Christopher J. Calhoun: Unlike many of the engineered therapies or allogenic cell therapies that typically require sophisticated and expensive manufacturing processes, Paracrine's Cell Therapy is produced in real-time using the Celution System. This enables a per-patient price point in the $6,000 (non-vascular) to $9,000 (vascular) range and provides a clear pharmacoeconomic benefit to patients, physicians, and payers.

Tuba: How has the capital raise process been for Paracrine in the past, and what is in store for the future?

Christopher J. Calhoun: This month, Paracrine is launching our Series A financing to bring in the necessary capital to fund the company and importantly, our clinical pipeline. Our laser-focused plan and extensive clinical experience, coupled with world-class clinical leadership in each of our trials and a lean, talented management team, distinguishes Paracrine as one of the most attractive investment opportunities in its field.

Tuba: Any plans on collaborations in the future?

Christopher J. Calhoun: Ischemia, inflammation, and tissue injury are common within many diseases and conditions, making our platform highly scalable across diverse therapeutic markets. Collaborations and partnerships are an essential part of our broader vision to expand and advance our clinical pipeline as well as to accelerate and broaden our reach into the market as we move closer to approval. Everything we do is a collaboration of sorts.

Tuba: What is the Chris Calhoun back story?

Christopher J. Calhoun: Christopher Calhoun is the inventor featured on 96 medical product patent applications. He has been involved in the research, medical device, and biotech industries for more than 25 years.

During his career, Calhoun has brought in more than $400 million and completed transactions with leading device and pharmaceutical companies including GE Healthcare, Olympus Medical, Medtronic, Astellas Pharma, Senko Medical, Kensey Nash, Green Hospital Supply, Lorem Vascular and Mast Biosurgery, as well as establishing a $106 million development contract with BARDA.

Calhoun has presented in more than 100 regenerative medicine, technology, and financial conferences, and he has been an invited lecturer in entrepreneurship and biotechnology.

Source: Business Insider

About Author: Christopher J. Calhoun is the CEO and President of Paracrine. Mr. Calhoun received a B.A. from the University of California, San Diego, and an M.B.A. from the University of Phoenix. Mr. Calhoun was also involved in research and management for the Plastic Surgery Bone Histology and Histometry Laboratory at the University of California, San Diego