HemAcure and Sernova, A Big Deal

Richard (Rick) Mills
Ahead of the Herd

As a general rule, the most successful man in life is the man who has the best information

When most of us suffer a cut cells in the blood, called platelets, go to where the cut is, plug the hole and stop the bleeding. While the platelets are plugging the hole they release chemicals that attract more of the ‘sticky’ platelets and twelve (numbered using Roman numerals I through XII) proteins in the blood known as clotting factors are activated. These proteins mix with the platelets to form fibers which make the clot stronger and stop the bleeding.

Having too little of factors VIII (8) or IX (9) is what causes hemophilia. A person with hemophilia will lack only one factor, either factor VIII or factor IX, but not both. There are two major kinds of hemophilia: hemophilia A, which is a factor VIII deficiency; and hemophilia B, which is a factor IX deficiency.

Hemophilia is a genetic disorder which means it’s the result of a change in genes that was either inherited (passed on from parent to child) or occurred during development in the womb. Although it is mostly passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a change in a gene. All races and ethnic groups are equally affected by hemophilia A. The disease almost always affects males but can also affect females.

Many people believe that hemophiliacs bleed a lot from minor cuts but external wounds are usually not that serious. Much more serious is internal hemorrhaging that can take place in joints (especially knees, ankles and elbows) and into tissues and muscles. Bleeding can also occur in vital organs putting a hemophiliac’s life in danger.

Although effective treatment of the symptoms is available, there is no cure for hemophilia A at present and therapy has to be individualized to specific patients. Patients have to get lifelong infusions with recombinant factor VIII (rFVIII) several times a week to compensate for the missing clotting factor.

The global total hemophilia market was valued at US$ 9.3 billion in 2015. Approximately 20,000 people in the United States, 10,000 in Europe and approximately 2,500 in Canada have a moderate or severe form of hemophilia A. Annual costs for the treatment of the disease for each patient may range from US$60,000 to US$260,000 for a total cost of between $2-5B per year just in North America and Europe.

Grand View Research

The Horizon 2020 program

Horizon 2020 is the largest European Union (EU) research and innovation program ever undertaken with nearly €80 billion of funding available over the seven years between 2014 to 2020. Horizon 2020 promises breakthroughs, discoveries and world firsts by taking great ideas from the lab to the market, for example in the field of personalized medicine providing novel therapies such as gene or cell therapy.

HemAcure project, a novel personalized medicine curative therapy

An international research consortium, under the name HemAcure unites scientific academic institutions from Germany, Italy, the UK and Sernova Corp from Canada.

The following institutions are involved in HemAcure:

  • ARTTIC, a Munich-based enterprise that specializes in the management of EU-funded collaborative research projects, is in charge of project management.
  • The Department of Tissue Engineering and Regenerative Medicine of the Wuerzburg University Hospital is responsible for isolating the cells.
  • The Università del Piemonte Orientale (Italy) is developing, optimizing and performing the gene correction of the patient cells for expression of the Factor VIII therapy.
  • Scientists from Loughborough University (UK) are focussing on the manufacturing process and safety testing.
  • Sernova a Canadian public company, is responsible for conducting the preclinical safety and efficacy studies with the Factor VIII producing cells in its proprietary Cell Pouch™ using a model of hemophilia developed by consortium partner Universita del Piemonte Orientale (Italy) in preparation for clinical trials.
  • The quality management (GMP processes) is being monitored by IMS – Integrierte Management Systeme in Heppenheim, Germany. The company acts as a point of contact for international projects in the pharmaceutical and medical engineering sector.

The overall objective of the HemAcure project is to develop and refine the tools and technologies for a novel, curative ex vivo (outside the body) prepared cell based therapy to treat hemophilia A that should ultimately lead to improved quality of life for patients. The EU’s Horizon 2020 programme has stage funded the HemAcure project with €5.5 million (Cdn$8.06M, US$6.3). The most recent tranche of funding has just been approved based on the encouraging results to date.

The consortium’s idea: A personalized medicine solution using the patients’ own cells (remember each patient has to have individualized therapy) which are genetically modified outside the body to produce the missing clotting factor using precursor cells of endothelial cells flowing in the bloodstream. After modification these cells are transplanted back into the patient’s body in Sernova Corp’s Cell Pouch™.

After Sernova’s Cell Pouch™ is implanted in the body and forms its unique vascularized tissue chambers, the genetically modified cells are then transplanted into the vascularized chambers and are expected to continuously produce the clotting factor and release it into the bloodstream for a long period of time. This should mitigate the disease’s impact noticeably, increase the patients’ quality of life and reduce the overall cost of therapy.

Sernova

Sernova Corp. (TSX-V: SVA) (OTCQB: SEOVF) (FSE: PSH), is a Canadian publically traded, clinical stage, regenerative medicine company developing an implantable, scalable device, the Cell Pouch System™ and therapeutic cells for the treatment of diseases such as diabetes, and hemophilia.

Sernova’s Cell Pouch™ forms a natural vascularized environment for long-term survival and function of the therapeutic cells which release into the bloodstream required but missing proteins or hormones.

Sernova’s Cell Pouch™ technology would be beneficial if it provided a simple reduction in the number of therapeutic injections a patient must take; however, there is the possibility that it could even essentially ‘cure’ the disease through natural release and regulation of the therapeutic proteins or hormones.

“Sernova has developed its proprietary highly innovative Cell Pouch technologies for the placement and long-term survival and function of immune protected therapeutic cells. It has proven to be safe and efficacious in multiple small and large animal preclinical models and has demonstrated safety alone and with therapeutic cells in a clinical trial in humans for another therapeutic indication (diabetes – editor). We believe the Cell Pouch platform is the first such patented technology proven to become incorporated with blood vessel enriched tissue-forming tissue chambers without fibrosis for the placement and long-term survival and function of immune protected therapeutic cells.” Sernova News Release, Marketwire – July 24, 2017

Sernova is today a relatively unknown pure regenerative medicine play that has partnered their Cell Pouch™ with a network of academic cell therapy research and development partners. Below is a HemAcure consortium approved news release issued by Sernova Corp. on Monday July 24, 2017.

It’s your authors opinion ‘relatively unknown’ is a term that will shortly no longer apply to Sernova Corp.

Sernova-HemAcure Consortium Announce Significant Progress in Development of ‘First in World’ Regenerative Medicine Therapy for Treatment of Hemophilia A Patients

Breakthrough scientific progress is made in development of a disruptive personalized regenerative medicine therapy within Sernova’s Cell Pouch(TM) for treatment of Hemophilia A validated by European Commission’s confirmation of next stage of funding of the €5.6Million EU Horizon 2020 Grant Award to the HemAcure Consortium

LONDON, ONTARIO – (Marketwire – July 24, 2017) – Sernova Corp. (TSX-V: SVA) (OTCQB: SEOVF) (FSE: PSH), a clinical stage regenerative medicine company, announced today significant scientific progress achieved in the development of a ‘first in world’ personalized regenerative medicine therapy for the treatment of Hemophilia A patients by the HemAcure Consortium and confirmation of the second phase of funding of the Consortium by the European Commission.

The therapy being developed by international scientific Consortium members consisting of three European academic institutions, an enterprise for quality management and Sernova Corp is to treat severe Hemophilia A, a serious genetic bleeding disorder caused by missing or defective clotting factor VIII in the blood stream. This therapy consists of Sernova’s implanted Cell Pouch(TM) device transplanted with therapeutic cells, corrected to produce Factor VIII at a level sufficient to significantly reduce the side effects of the disease and improve patient quality of life.

“The international HemAcure Consortium team members are pleased with the ground breaking scientific advances achieved at this point and are on track for this regenerative medicine solution to advance into human clinical evaluation,” remarked Dr. Philip Toleikis, Sernova President and CEO.

Toleikis added, “Sernova’s Cell Pouch platform technologies are achieving important world first milestones in both diabetes and now hemophilia, two significant clinical indications which are being disrupted by its regenerative medicine approach aimed at significantly improving patient quality of life.”

“We are thrilled with the approval by the European Union of the next stage of funding for the HemAcure program based on our quality interim report. This is a strong validation of the Consortium’s dedication and teamwork and the importance of this regenerative medicine approach,” said Dr. Joris Braspenning, HemAcure Program Coordinator.

In summary, the following ground-breaking developments have been achieved by the Consortium:

  • A reliable procedure has been implemented to isolate and maintain required endothelial cells from a sample of the patient’s blood.
  • Using a novel gene correction process, the cells have been corrected and tuned to reliably produce the required Factor VIII to treat Hemophilia A.
  • The cells have been successfully scaled up to achieve the required therapeutic number, and cryopreserved for shipping and future transplant into the implanted Cell Pouch.
  • A preliminary study confirmed survival of the Factor VIII corrected human cells injected into the hemophilia model, achieving sustained therapeutic Factor VIII levels. This preliminary work is being used to aid in dosing of these cells in the Cell Pouch.
  • Safe Cell Pouch surgical implant and cell transplant procedures have been developed in the hemophilia A model in preparation for use in hemophilia patients.
  • Development of Cell Pouch vascularized tissue chambers suitable for Factor VIII producing cell transplant has been demonstrated in the hemophilia A model, expected to mimic the predicted findings in human patients.
  • In combination, this work is in preparation for safety and efficacy studies of the human hemophilia corrected Factor VIII producing cells in the Cell Pouch in a preclinical model of hemophilia.

This combination of advances by the HemAcure team represents a ‘first in world’ achievement towards developing a regenerative medicine therapy for the treatment of severe hemophilia A patients.

“In this regard, these fundamental advancements have set the stage for further optimization and implementation of cell production processes under controlled GMP conditions,” stated Martin Zierau, IMS member consortium team leader responsible for coordination of GMP processes.

With Factor VIII corrected cells, studies are ongoing to optimize cell dosing within the Cell Pouch and for study of safety and efficacy of hemophilia corrected Factor VIII cells in the hemophilia model. These studies are in support of the current extensive regulatory package already assembled for the Cell Pouch in anticipation of human clinical evaluation of the Cell Pouch with hemophilia corrected Factor VIII producing cells.

A big deal

Any discussions regarding advancing HemAcure’s plan, and more funding from Horizon 2020, had to be centered around success in these three areas:

  • CELLS ARE PRODUCING FACTOR VIII: The Consortium has successfully developed the process for isolating and maintaining the required cells from a sample of patient’s blood. Using a special technique these cells have been corrected and tuned to produce Factor VIII on a constant basis.
  • CORRECTED CELLS HAVE BEEN SCALED UP: The corrected cells have then been multiplied to demonstrate that the required number of cells can be produced. After testing, batches of corrected cells have been frozen, stored for later transplantation and successfully shipped, thawed and recovered. With further optimization and GMP production, this being the process anticipated to be used for future treatment of patients with hemophilia A.
  • CELLS PRODUCING THERAPEUTIC BLOOD LEVELS OF FACTOR VIII: In further preclinical tests, in a preliminary study, Factor VIII producing cells have been shown to produce therapeutic blood levels of Factor VIII. Studies have already shown that the Cell Pouch can produce vascularized tissue chambers in the hemophilia model and further studies will optimize dosing of hemophilic patient corrected cells that will then be transplanted into the Cell Pouch™ for evaluation of safety and efficacy in the preclinical model of hemophilia.

Conclusion

Being that all the companies in the HemAcure consortium are private, except SVA, and that they plan on ‘bringing breakthroughs, discoveries and world firsts from the lab to the market’ might not Sernova be a great way to leverage this in your portfolio?

And SVA is no one trick pony, the company is a leader in the regenerative space with their Cell Pouch™ and upon FDA clearance plan to initiate clinical trials in the United States for diabetes – expected to start patient enrollment this fall.

Add in developing local immune protection technology within the Cell Pouch™ and the company’s very own glucose responsive stem cell technology, you can see why your author thinks Sernova Corp might just be the best regenerative medicine pure play out there.

All of these reasons are why Sernova Corp. is on my radar screen. Is SVA on yours?

If not, maybe it should be.

Richard (Rick) Mills

aheadoftheherd.com

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Legal Notice / Disclaimer- This article is not and should not be construed as an offer to sell or the solicitation of an offer to purchase or subscribe for any investment.

Consortium Focused on Hemophilia A Patients, Announces Significant Progress in Development of ‘First in World’ Regenerative Medicine Therapy

Sernova Corp, an Ontario-based clinical stage regenerative medicine company, reported significant scientific progress achieved in the development of a ‘first in world’ personalized regenerative medicine therapy for the treatment of Hemophilia A patients by the HemAcure Consortium and confirmation of the second phase of funding of the Consortium by the European Commission.

The therapy being developed by international scientific Consortium members consisting of three European academic institutions, an enterprise for quality management and Sernova Corp is to treat severe Hemophilia A, a serious genetic bleeding disorder caused by missing or defective clotting factor VIII in the blood stream. This therapy consists of Sernova’s implanted Cell Pouch(TM) device transplanted with therapeutic cells, corrected to produce Factor VIII at a level sufficient to significantly reduce the side effects of the disease and improve patient quality of life.

HemAcure is the name of the consortium developing a product for hemophilia A. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 667421. The consortium members include the University Hospital Wuerzburg (Coordinating Institute), Germany, IMS – Integrierte Management, Heppenheim, Germany, Università del Piemonte Orientale “Amedeo Avogadro,” Novara, Italy, Loughborough University, Loughborough, United Kingdom, ARTTIC International Management Services, Munich, Germany and Sernova Corp., London, Ontario, Canada.

The main objective of the HemAcure project is to develop and refine the tools and technologies for a novel ex vivo prepared cell based therapy within Sernova’s prevascularized Cell Pouch to treat this bleeding disorder that should ultimately lead to improved quality of life of the patients.

“We are thrilled with the approval by the European Union of the next stage of funding for the HemAcure program based on our quality interim report. This is a strong validation of the Consortium’s dedication and teamwork and the importance of this regenerative medicine approach,” said Dr. Joris Braspenning, HemAcure Program Coordinator.

 “The international HemAcure Consortium team members are pleased with the ground breaking scientific advances achieved at this point and are on track for this regenerative medicine solution to advance into human clinical evaluation,” remarked Dr. Philip Toleikis, Sernova President and CEO.  Toleikis added, “Sernova’s Cell Pouch platform technologies are achieving important world first milestones in both diabetes and now hemophilia, two significant clinical indications which are being disrupted by its regenerative medicine approach aimed at significantly improving patient quality of life.”

In summary, the following ground-breaking developments have been achieved by the Consortium:

  • A reliable procedure has been implemented to isolate and maintain required endothelial cells from a sample of the patient’s blood.
  • Using a novel gene correction process, the cells have been corrected and tuned to reliably produce the required Factor VIII to treat Hemophilia A.
  • The cells have been successfully scaled up to achieve the required therapeutic number, and cryopreserved for shipping and future transplant into the implanted Cell Pouch.
  • A preliminary study confirmed survival of the Factor VIII corrected human cells injected into the hemophilia model, achieving sustained therapeutic Factor VIII levels. This preliminary work is being used to aid in dosing of these cells in the Cell Pouch.
  • Safe Cell Pouch surgical implant and cell transplant procedures have been developed in the hemophilia A model in preparation for use in hemophilia patients.
  • Development of Cell Pouch vascularized tissue chambers suitable for Factor VIII producing cell transplant has been demonstrated in the hemophilia A model, expected to mimic the predicted findings in human patients.
  • In combination, this work is in preparation for safety and efficacy studies of the human hemophilia corrected Factor VIII producing cells in the Cell Pouch in a preclinical model of hemophilia.

This combination of advances by the HemAcure team represents a ‘first in world’ achievement towards developing a regenerative medicine therapy for the treatment of severe hemophilia A patients. “In this regard, these fundamental advancements have set the stage for further optimization and implementation of cell production processes under controlled GMP conditions,” stated Martin Zierau, IMS member consortium team leader responsible for coordination of GMP processes. With Factor VIII corrected cells, studies are ongoing to optimize cell dosing within the Cell Pouch and for study of safety and efficacy of hemophilia corrected Factor VIII cells in the hemophilia model. These studies are in support of the current extensive regulatory package already assembled for the Cell Pouch in anticipation of human clinical evaluation of the Cell Pouch with hemophilia corrected Factor VIII producing cells.

Sernova has developed its proprietary highly innovative Cell Pouch technologies for the placement and long-term survival and function of immune protected therapeutic cells. It has proven to be safe and efficacious in multiple small and large animal preclinical models and has demonstrated safety alone and with therapeutic cells in a clinical trial in humans for another therapeutic indication. We believe the Cell Pouch platform is the first such patented technology proven to become incorporated with blood vessel enriched tissue-forming tissue chambers without fibrosis for the placement and long-term survival and function of immune protected therapeutic cells.

People with Hemophilia have prolonged abnormal bleeding as a result of trauma. Hemophilia A, also called factor VIII (FVIII) deficiency is the most common form of Hemophilia and is a genetic disorder caused by missing or defective FVIII, a blood clotting protein. Severe hemophilia occurs in about 60% of cases where the deficiency of FVIII is less than 1% of normal blood concentration. While it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous change in the gene. According to the US Centers for Disease Control and Prevention hemophilia occurs in about 1 in 5,000 births. If the prolonged bleeding occurs in the brain of a person with hemophilia, it can be fatal. Prolonged bleeding in joints can cause inflammatory responses and permanent joint damage. Approximately 20,000 people in the United States and 10,000 in Europe have the moderate or severe form of hemophilia A, as well as approximately 2,500 in Canada. All races and ethnic groups are equally affected by hemophilia A. Though there is no cure for the disease, it can be controlled with regular infusions of recombinant clotting FVIII. Annual costs for the treatment of the disease for each patient may range from $60,000 to $260,000 US for a total cost of between $2-5B per year in North America and Europe.

Horizon 2020 is the biggest EU Research and Innovation program ever with nearly €80 billion of funding available over seven years (2014 to 2020). It promises more breakthroughs, discoveries and world-firsts by taking great ideas from the lab to the market. The project is funded as part of societal challenges “personalizing health and care” in a specific call about innovative treatments and technologies. New therapies, such as gene or cell therapies, often require technological innovation in the form of development of specific component tools and techniques such as isolation and multiplication of a cell or development of a scaffold, delivery of the therapy to the patient and for following-up the effect of the therapy in the patient. In particular, achieving therapeutic scale production and GMP standards at reasonable cost is often underestimated. The European Union aims to improve the development of advanced methods and devices for targeted and controlled delivery, and to bring these innovative treatments to the patient.

Sangamo Therapeutics and Pfizer Announce Collaboration for Hemophilia A Gene Therapy

Sangamo Therapeutics, Inc. and Pfizer Inc. announced this week, an exclusive, global collaboration and license agreement for the development and commercialization of gene therapy programs for Hemophilia A, including SB-525, one of Sangamo’s four lead product candidates, which Sangamo expects will enter the clinic this quarter.

“Sangamo brings deep scientific and technical expertise across multiple genomic platforms, and we look forward to working together to advance this potentially transformative treatment for patients living with Hemophilia A,” said Mikael Dolsten, MD, PhD, President of Worldwide Research and Development at Pfizer. “Pfizer has made significant investments in gene therapy over the last few years and we are building an industry-leading expertise in recombinant adeno-associated virus (rAAV) vector design and manufacturing. We believe SB-525 has the potential to be a best-in-class therapy that may provide patients with stable and durable levels of Factor VIII protein with a single administration treatment.”

“With a long-standing heritage in rare disease, including hemophilia, Pfizer is an ideal partner for our Hemophilia A program,” said Dr. Sandy Macrae, Sangamo’s Chief Executive Officer. “We believe Pfizer’s end-to-end gene therapy capabilities will enable comprehensive development and commercialization of SB-525, which could potentially benefit Hemophilia A patients around the world. This collaboration also marks an important milestone for Sangamo as we continue to make progress in the translation of our ground-breaking research into new genomic therapies to treat serious, genetically tractable diseases.”

Under the terms of the collaboration agreement, Sangamo will receive a $70 million upfront payment from Pfizer. Sangamo will be responsible for conducting the SB-525 Phase 1/2 clinical study and certain manufacturing activities. Pfizer will be operationally and financially responsible for subsequent research, development, manufacturing and commercialization activities for SB-525 and additional products, if any. Sangamo is eligible to receive potential milestone payments of up to $475 million, including up to $300 million for the development and commercialization of SB-525 and up to $175 million for additional Hemophilia A gene therapy product candidates that may be developed under the collaboration. Sangamo will also receive tiered double-digit royalties on net sales. Additionally, Sangamo will be collaborating with Pfizer on manufacturing and technical operations utilizing viral delivery vectors.

Gene therapy is a potentially transformational technology for patients, focused on highly specialized, one-time, treatments that address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patient’s cells to compensate for a defective one. The genetic material can be delivered to the cells by a variety of means, most frequently using a viral vector such as rAAV. There have been no gene therapy products approved in the U.S. to date.

Hemophilia A is a rare blood disorder caused by a genetic mutation resulting in insufficient activity of Factor VIII, a blood clotting protein the body uses to stop bleeding. There are approximately 16,000 patients in the U.S. and more than 150,000 worldwide with Hemophilia A. SB-525 is comprised of a rAAV vector carrying a Factor VIII gene construct driven by a proprietary, synthetic, liver-specific promoter. The U.S. Food and Drug Administration has cleared initiation of human clinical trials for SB-525, which also has been granted orphan drug designation. Sangamo is on track this quarter to start a Phase 1/2 clinical trial to evaluate safety and to measure blood levels of Factor VIII protein and other efficacy endpoints.