On July 1, 2021 Exacis Biotherapeutics, Inc., a development-stage immuno-oncology company working to harness the immune system to cure cancer, reported two significant advances in its manufacturing capabilities. Exacis’ is partnering with parent Factor Bioscience to produce its iPSC-derived CAR-T and NK cells within a GMP cleanroom facility built by Factor, and Exacis has hired Bryan Jones PhD as its Head of Technical Operations.

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Exacis’ parent company, Factor Bioscience, recently completed construction of a 5,000 square foot GMP cleanroom facility at its Cambridge, Massachusetts headquarters. The facility includes two ISO Class 7 cleanrooms and is designed to enable production of advanced mRNA, gene-editing, and cell therapy products to support all phases of clinical development. Exacis will use this new facility to produce its allogeneic mRNA engineered cell-therapy product candidates for non-clinical and clinical testing.

Exacis’ next generation approach avoids the use of DNA and viruses and instead uses proprietary, innovative mRNA-based technology. This technology is used for generating iPSCs and for performing gene editing to create potent, targeted, allogeneic (off-the-shelf) cell therapy products, termed ExaCAR-T and ExaCAR-NK cells. The company anticipates that the Factor GMP cleanroom facility will have sufficient capacity to support its programs through late-stage clinical development.

Matthew Angel, PhD, CEO of Factor Bioscience, Exacis’ parent company, added, "We invested in constructing our GMP cleanroom facility to give our partners more control over the manufacturing aspects of their cell-therapy programs. We look forward to supporting Exacis as it advances its engineered NK-cell and T-cell programs through clinical development."

Bryan Jones, PhD, Head of Technical Operations

Dr. Jones joins the company with 30 years of drug development experience in a variety of roles including at the C-suite level which allows him to contribute across many dimensions. Most recently, he was Chief Operating Officer at Sollis Therapeutics. Immediately prior, he was Vice President of Operations at Sorrento Therapeutics, a leading therapeutic antibody company and one of the early adopters of cell therapy. Dr. Jones will oversee the buildout of the Manufacturing and Quality Operations working alongside Factor Bioscience in the new facility. "The high cost and long lead times required for cell therapy manufacturing are major issues that have hindered the progress of developing new treatments," said Dr. Jones. "The Exacis technology brings several significant advances that will allow for greater adoption of these highly targeted medicines."

Exacis CEO Gregory Fiore MD commented, "We are excited to announce these major steps forward in our ability to maintain control of our own cell supply and its quality. Adding Bryan as head of Technical Operations and securing a dedicated GMP manufacturing capacity within the Factor facility allows us to produce our unique and high quality cells on our own timeline as we progress toward the clinic."

On July 1, 2021 Epigenomics AG (Frankfurt Prime Standard: ECX, OTCQX: EPGNY; the "Company") reported that has entered into an agreement with its shareholder Deutsche Balaton Aktiengesellschaft ("Balaton") on June 11, 2021, under which Balaton is obligated to underwrite a mandatory convertible bond to be issued by the Company in an aggregate principal amount of up to EUR 18,150,000.00 by exercising its subscription rights and by acquiring notes which have not been subscribed by the shareholders in the subscription offer ("back-stop agreement") (Press release, Epigenomics, JUL 1, 2021, View Source [SID1234584591]). For further information on the mandatory convertible bond and the back-stop agreement, please refer to the ad hoc announcement.

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In order to provide the shareholders of the Company with a complete picture, the Company informs in addition to the ad hoc announcement that Balaton is indirectly controlled by Mr. Wilhelm K. T. Zours according to the voting rights announcement published on May 27, 2021. According to the same voting rights announcement, Mr. Wilhelm K. T. Zours indirectly controls 23.02% of the Company’s voting rights via Balaton and other companies directly and indirectly controlled by him. On this basis, the Company assumes as a precautionary measure that Mr. Wilhelm K. T. Zours, and thus also Balaton, are related parties of the Company pursuant to Section 111a (1) sentence 2 AktG.

In this context, the Company announces that, pursuant to the back-stop agreement, it is obliged to offer the notes not subscribed by the other shareholders to Balaton for purchase. In return for its obligations to exercise its subscription right and to acquire the notes not subscribed by the other shareholders, Balaton is further entitled to a commission in the amount of 3.5% of the maximum total subscription price of EUR 18,150,000.00, i.e. in the amount of EUR 635,250.00. The Company is entitled to terminate the back-stop agreement with Balaton or, subject to certain conditions, to reduce the commission payable to Balaton if a third party offers to enter into the obligation with the Company to purchase the notes not subscribed by the remaining shareholders at a lower commission.

The Executive Board assesses the terms of the back-stop agreement as appropriate. The Supervisory Board approved the conclusion of the back-stop agreement on June 11, 2021.

On July 1, 2021 PDX Pharmaceuticals reported that in collaboration with OHSU, has received a perfect score on its fast track SBIR grant application to the NCI. The application focuses on development of ARACTM pipeline. Grant title: Novel Nano-immunotherapy for Treatment of Non-small Cell Lung Cancer, requested budget of $2.26 M over 3 years.

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Furthermore, the team scored very high (18) on its direct phase II SBIR grant application to the NCI. The application focuses on IND enabling studies of AIRISETM pipeline. Grant title: In Situ Tumor Vaccination with a Nano-oligo Therapeutic to Induce Whole-body Antitumor Immune Response, requested budget of $2.15 M over 1.5 years .

The current NCI-SBIR payline is 22 and below. Therefore, we anticipate both applications will be awarded (pending council review).

ARACTM stands for Antigen Release Agent and Checkpoint Inhibitor

AIRISETM stands for Augmenting Immune Responses and Inhibiting the Suppressive Environment of Tumors

On July 1, 2021 Wugen reported that An immunotherapy based on supercharging the immune system’s natural killer cells has been effective in treating patients with recurrent leukemia and other difficult to treat blood cancers (Press release, Wugen, JUL 1, 2021, View Source [SID1234584574]). Now, researchers at Washington University School of Medicine in St. Louis have shown in preclinical studies conducted in mice and human cells that this type of cell-based immunotherapy also could be effective against solid tumors, starting with melanoma, a type of skin cancer that can be deadly if not caught early.

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The study is published June 29 in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

In recent years, an immunotherapy called immune checkpoint inhibitors has revolutionized treatment for advanced melanoma. In one well-known example, this immunotherapy was successfully used to treat former President Jimmy Carter, whose melanoma had spread to his liver and brain.

But the therapy only works in about half of such patients. And even among those who respond well to the initial therapy, about half go on to develop resistance to it. Consequently, researchers have been seeking different ways to harness the immune system to attack melanoma cells. One possibility is to use natural killer (NK) cells, a part of the immune system’s first line of defense against dangerous cells, whether cancer cells or invading bacteria.

Todd A. Fehniger, MD, PhD, a professor of medicine, and his team have had success in clinical trials treating recurrent leukemia with a patient’s own natural killer cells or those from a donor. The NK cells are harvested from the patient’s or a donor’s blood and exposed to a set of chemical signals called cytokines that activate the cells and prime them to remember this activation. When these "cytokine-induced memory-like" NK cells are given to the patient, they are more potent in attacking the cancer because they already have been revved up, as Fehniger puts it.

"These ‘revved-up’ memory-like NK cells attack blood cancers quite well," said Fehniger, the study’s co-senior author and an oncologist who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. "But relatively little work has been done on whether these cells can be used against solid tumors. This is an unmet need in solid tumor oncology. Our study provides proof of principle that memory-like NK cells respond better than normal NK cells against melanoma, and it serves as a stepping stone to a first-in-human clinical trial of these cells in advanced melanoma."

Added co-senior author Ryan C. Fields, MD, the Kim and Tim Eberlein Distinguished Professor of Surgical Oncology: "We hope this is also a step toward harnessing NK cells against multiple solid tumors. Melanoma was a good place to start because we know it responds to immune therapy. But because many patients don’t respond or develop resistance, we felt that targeting a different aspect of the immune system was a promising strategy to pursue."

The standard checkpoint inhibitor immunotherapy that works well in some melanoma patients targets T cells, another type of immune cell that also frequently is harnessed against different forms of cancer. According to the researchers, patients who don’t respond well or stop responding to the T cell-based standard therapy and have no other options would be good candidates for NK cell therapy.

The researchers studied human NK cells from both healthy people and from patients with melanoma and found that the cytokine-induced memory-like NK cells could effectively treat mice harboring human melanoma tumors. Tumors shrank to the point of being almost undetectable in many of the mice, and the memory-like NK cells prevented the tumors from returning in most cases for the duration of the 21-day experiment. While normal NK cells also reduced and controlled melanoma tumors, they did not do so to the same degree.

"We are currently designing a clinical trial to evaluate these NK cells in patients with advanced melanoma who have exhausted all other treatment options," Fehniger said. "We would like to investigate NK cells from a donor and, separately, a patient’s own NK cells to see if the cytokine-induced memory-like NK cells offer an effective treatment option for patients with this aggressive skin cancer."

The NK cell-based immunotherapy is potentially safer than other cell-based immunotherapies because the NK cells do not trigger a cytokine storm, as is seen sometimes in CAR-T cell therapy, which often is used for blood cancers, nor do the NK cells cause graft-versus-host disease, which sometimes follows a stem cell transplant.

"Even 10 years ago, we had no effective therapies for advanced melanoma — much like the lack of therapies for glioblastoma or advanced pancreatic cancer today," said Fields, a surgeon who treats patients at Siteman. "Checkpoint immunotherapy has revolutionized melanoma treatment, but we’re still not satisfied with the 50% response rate. We want to do better, and this NK cell therapy is a promising approach. And in the future, we may be able to combine an NK cell-based therapy with checkpoint inhibition for an even better response."

Fehniger and his colleagues have worked with Washington University’s Office of Technology Management to license the cytokine-induced memory-like NK cell technology to a company called Wugen. Fehniger is a co-founder of Wugen and serves on its scientific advisory board.

On July 1, 2021 Caribou Biosciences reported that it filed on Thursday to raise $100 million in its Wall Street debut (Press release, Caribou Biosciences, JUL 1, 2021, View Source [SID1234584565]). The proceeds will propel three off-the-shelf CAR-T therapies into and through the clinic and boost Caribou’s work in natural killer (NK) cell therapies.

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Caribou is developing all three programs for patients with blood cancers whose disease has come back despite undergoing other treatments or did not respond to those treatments in the first place.

The company’s most advanced program, CB-010, is an anti-CD19 CAR-T that’s in a phase 1 trial in B-cell non-Hodgkin lymphoma. Some of the IPO proceeds will support this trial through initial data, which are expected in 2022.

RELATED: Caribou nets $115M to boost CRISPR tech, advance off-the-shelf cell therapies

The funds will also bankroll IND-enabling activities for two other programs: CB-011, a BCMA-targeting CAR-T in development for the treatment of multiple myeloma and CB-012, a CAR-T targeting CD371 for the treatment of acute myeloid leukemia. The company hopes to start human trials for these programs in 2022 and 2023, respectively.

All three programs are allogeneic CAR-T treatments, meaning they are made from donor cells, rather than a patient’s own cells like the four approved CAR-T therapies from Novartis, Gilead’s Kite unit and Bristol Myers Squibb.

Those types of treatments, called autologous, can be complex and time-consuming to make: cells must be taken out of the patient, modified to fight cancer and then put back into the patient. Some patients don’t have enough T cells, or T cells of good enough quality, to make those treatments. Others simply don’t have much time.

RELATED: Blackstone, Cellex and Intellia form $250M CAR-T startup

Though Caribou’s CAR-T programs all target blood cancer, the company is working on allogeneic NK cell therapies based on induced pluripotent stem cells for solid tumors. Some of the IPO haul will support R&D in this area, as well as the development of the CRISPR technology it uses to make its cell therapies.

In recent years, the cell therapy space has been teeming with new entrants looking to break the barriers seen in the first generation of cell therapies. In 2018, a pair of former Kite Pharma executives unveiled Allogene, a biotech that started out with $300 million and 17 off-the-shelf CAR-T assets licensed from Pfizer.

France-based Mnemo Therapeutics is trying to make CAR-T work for solid tumors by identifying better targets. Other companies, like Catamaran Bio, are going after that same piece of the pie, but via NK cell treatments instead.