On October 5, 2020 ORPHELIA Pharma, a French biopharmaceutical company dedicated to the development and marketing of pediatric and orphan drugs reported the inclusion of the first-in patient in a clinical study aimed at demonstrating the bioequivalence between Kimozo, the first pediatric formulation of temozolomide under clinical development, and Temodal capsule (Press release, ORPHELIA Pharma, OCT 5, 2020, View Source [SID1234568070]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Although not approved in this indication, temozolomide is an essential anticancer medicine recommended for use in treatment protocols of relapsed or refractory neuroblastoma, a condition that affects young children. However, the only oral formulations that are commercially available are in the form of capsules that are poorly adapted to children. Caretakers are thus compelled to open capsules and disperse the content into a soft food prior to administration to the child, which harbors several risks such as the uncertainty with regards to the delivered dose, the exposure of the caregiver to the cytotoxic drug and the instability of the drug in aqueous milieu. To overcome the risks this situation implies, Kimozo, a ready to use oral formulation has been specifically designed to address the needs of the pediatric population.

Kimozo has been developed in collaboration with Gustave Roussy, one of the leading cancer centers in Europe. The current clinical trial conducted by ORPHELIA Pharma aims at demonstrating, first for regulatory purposes, the bioequivalence between Kimozo and the Temodal capsules in adult patients having brain cancers, with additional clinical investigation to come in the pediatric population of interest.

"We have reached an important milestone for Kimozo with the clinical trial approval from competent authorities and the recruitment of a first patient", said Caroline Lemarchand, Chief Pharmaceutical Development Officer of ORPHELIA Pharma "We plan to enroll 30 patients by mid-2021 thanks to the support of the three neuro-oncology teams involved in the study: Professor Ducray of the Hospices Civils de Lyon (coordinating investigator), Professor Chinot of the Timone Hospital in Marseille and Dr Bronnimann of Saint-André Hospital in Bordeaux. "

"We are pleased to contribute to the development of this new pediatric formulation of temozolomide. A liquid form is unambiguously of interest for treating children.", underlines Pr. François Ducray. Hugues Bienaymé, General Manager of ORPHELIA Pharma further comments: "This first administration is a major milestone in the development of Kimozo. We are now preparing the opening of our second clinical trial, which will evaluate Kimozo in pediatric patients, by the end of the year ", he concludes.

About the Bioequivalence Study (NCT04467346)

The clinical trial entitled "Bioequivalence Study between temozolomide oral suspension (Ped-TMZ) and Temodal capsules" (NCT04467346) is an open label phase I study, randomized, crossover, 2-period study in 30 male/female patients with primary CNS malignancies. Patients will receive, under fasting conditions, 200 mg/m² of Temozolomide Oral Suspension (Ped-TMZ, the code name of Kimozo) or Temodal, as single oral administration in 2 different study periods depending on the randomization, with no wash out period between administrations. The primary objective is to evaluate the bioequivalence between Kimozo and Temodal capsules for oral administration. The secondary objectives are to define the pharmacokinetic parameters of Kimozo administration and to assess its buccal safety.

The clinical centers are Hospices Civils de Lyon, Bron, France ; CHU de Bordeaux, Bordeaux, France and Hôpital de la Timone (AP-HM), Marseille, France. The Study sponsor is ORPHELIA Pharma.

About Kimozo

Kimozo (also known as ORP-005 or Ped-TMZ) is a ready-to-use and taste-masked oral suspension of temozolomide that is currently under development to address children needs. Kimozo is an investigational medicinal product not yet approved for marketing anywhere in the world.

On October 2, 2020 Celex Oncology reported strong new data that confirms that its patent protected solution of combining a sodium channel blocker with a potassium channel opener produces an enhanced response in inhibiting metastatic invasion in cancer cells (Press release, CELEX Oncology, OCT 2, 2020, View Source [SID1234632186]). Today’s data also reinforces the Company’s earlier findings of inhibiting metastatic invasion by blocking voltagegated sodium channels.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The company’s CEO and Professor Mustafa Djamgoz said "the new results are significant because they further underline and strengthen the potential of the new cancer treatment mechanism that we are developing in clinical trials".

The new data will make it possible to create a novel drug composition that will give the company’s drug candidates a prolonged patent life, and can benefit patients with a superior second-generation drug.

As reported earlier, the Celex mechanism appears to be present in in many (if not all) of the most commonly occurring cancer forms and as a result can offer a significant breakthrough in the treatment of major cancers. The Company’s CEO and Professor Mustafa Djamgoz adds "This means our treatment has the potential to benefit millions of patients around the world both as a stand-alone treatment or in combination with existing treatments." The Company expects this new development to have wide-ranging impact in clinical oncology.

On October 2, 2020 Race Oncology Limited reported that Professor Borje S. Andersson has agreed to join Race as Chief Medical Officer and Executive Director (Press release, Race Oncology, OCT 2, 2020, View Source [SID1234568216]). Under this role, Prof. Andersson will be responsible for progressing Race’s clinical development plans for Bisantrene. He will continue to Chair Race’s Clinical Advisory Board and provide ongoing clinical guidance, leadership and counsel to the Race Oncology Board.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Prof. Andersson was initially engaged as a scientific and clinical consultant to Race in January 2019, before becoming Chair of RAC’s Clinical Advisory Board on 5 December 2019. He joined the Race Board as a Non-Executive Director in January 2020.

Prof. Andersson is a world-recognised research leader in the field of leukaemia and stem cell transplantation at the MD Anderson Cancer Center in Houston, Texas. He is the inventor of IV Busulfan, an FDA-approved drug used in stem cell transplantation. Busulfan was approved in 1999 and has drastically improved survival for patients with leukemias, malignant lymphomas and genetic disorders amenable to stem cell transplantation, helping to reduce the death rate in the first 100 days after transplant from 30-40% to less than 3%.

Chairman, Dr John Cullity commented, "We are very fortunate to have secured this commitment from Borje to join Race as our Chief Medical Officer. The expertise Borje brings in understanding the patient experience and clinical approaches towards drug utilisation will be invaluable to how we structure our clinical development plans for Bisantrene. He continues to make his substantial international network of experts available and we have already significantly benefited from this. I am delighted to welcome Borje to this new role."

Phil Lynch, CEO and Managing Director said, "It is a privilege to have Borje’s guidance and leadership available to us at the Executive team level. As we move forward with our Bisantrene clinical strategy and our clinical workload increases, his CMO appointment provides us with additional expert resource to progress our clinical plans toward commercial outcomes."

Professor Andersson commented, "My experience with Race through the Clinical Advisory Board and Board roles has motivated me to seek broader engagement, and to more directly support the team to progress and optimise our strategic plans. I’m very excited to assume this new and expanded role that the Board has offered me."

On October 2, 2020 Foghorn Therapeutics, a preclinical biotech developing gene therapies for hematologic cancers and solid tumors, reported that it filed on Friday with the SEC to raise up to $100 million in an initial public offering (Press release, Foghorn Therapeutics, OCT 2, 2020, View Source [SID1234568140]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Foghorn is developing a new class of medicines targeting genetically determined dependencies within the chromatin regulatory system through its proprietary Gene Traffic Control platform. The company’s two most advanced candidates are FHD-286, a selective allosteric ATPase inhibitor, and FHD-609, a protein degrader. The candidates are being developed for hematologic cancers and solid tumors, and the company plans to file INDs for FHD-286 and FHD-609 in the 4Q20 and 1H21, respectively.

The Cambridge, MA-based company was founded in 2015 and plans to list on the Nasdaq under the symbol FHTX. Goldman Sachs, Morgan Stanley, Cowen and Wedbush PacGrow are joint bookrunners on the deal. No pricing terms were disclosed.

The article Preclinical oncology biotech Foghorn Therapeutics files for a $100 million IPO originally appeared on IPO investment manager Renaissance Capital’s web site renaissancecapital.com.

Investment Disclosure: The information and opinions expressed herein were prepared by Renaissance Capital’s research analysts and do not constitute an offer to buy or sell any security. Renaissance Capital’s Renaissance IPO ETF (symbol: IPO), Renaissance International ETF (symbol: IPOS), or separately managed institutional accounts may have investments in securities of companies mentioned.

The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.

On October 2, 2020 University of California San Francisco reported that Though cancer immunotherapy has become a promising standard-of-care treatment – and in some cases, perhaps a cure – for a wide variety of different cancers, it doesn’t work for everyone, and researchers have increasingly turned their attention to understanding why (Press release, University of California San Francisco, OCT 2, 2020, View Source [SID1234568068]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

For example, doctors have noticed that patients who initially respond well to the immunotherapy drugs known as checkpoint inhibitors, such as those that target a protein called PD-1, can develop resistance to these therapies if their cancer has metastasized from its initial location to form additional tumors in the liver – even if their primary cancer is quite distant from the liver.

In a new study published Oct. 2 in Science Immunology, a UC San Francisco research team led by Hematology and Oncology Clinical Fellow James Lee, MD, MHS, used a unique mouse model to figure out how this happens.

Then, the researchers, including senior author Jeffrey Bluestone, PhD, adjunct professor of microbiology and immunology and the A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology, showed that adding a second type of checkpoint inhibitor in a combination therapy can overcome this resistance, and might significantly increase the effectiveness of immunotherapy in patients with liver metastases.

"The liver actually triggers differences in immune cells at distant sites," Lee said. And what’s more, he added, "the liver can choose its enemy – what it wants to protect or not protect."

Cancers are sometimes able to avoid detection within the body by cloaking themselves from the immune system. They can produce large quantities of proteins like PD-L1, which "switch off" cells called regulatory T cells (Tregs; pronounced "tee-regs"), in turn tamping down the immune response of other T cells that attack cancer. Some checkpoint inhibitors counteract this cloaking process by preventing PD-L1 from binding to the PD-1 off-switches on T cells, allowing a normal defensive immune response against cancer cells.

The liver, which is tasked with filtering large quantities of blood directly from the digestive system and the rest of the body, plays an unexpectedly large role in regulating the immune system – specifically, by signaling which of the scavenged proteins it encounters as it does its job are from hostile invaders and which should be ignored.

In work supported by the Parker Institute for Cancer Immunotherapy, the scientists simulated metastasis by implanting mice with cancer cells in two separate locations, first under the skin and in then either the liver or the lung. They found evidence that when cancer takes hold in the liver it is "uniquely suppressive," said Lee – able to harness the liver’s powers to retrain the immune system and exert its influence on the immune response to related cancers that are distant in the body.

Compared to mice with secondary cancers implanted in the lung, survival rates were significantly worse in mice with secondary liver cancers after anti-PD-1 treatment: the immune system did not learn to recognize the liver tumor or, notably, the related tumor implanted under the skin.

That level of immune-system discernment clued the team in on a possible mechanism, because "only a few types of cells can be that specific in regulating the immune system," Lee said, including Tregs. Bluestone has spent decades studying these cells, and that’s where the researchers looked for an explanation. Could a liver tumor change the response of Tregs, and thus other T cells, to a separate, but related, tumor?

Using single-cell analyses, the team showed that, in mice with liver tumors, T cells associated with the related "primary" tumor were not as highly activated. Finally, the researchers showed that liver tumors change which genes are expressed in Tregs and, through those cells, a host of other immune-system cells as well. "It turned out that there wasn’t a difference in the quantity of Tregs between the skin tumors of mice with liver cancers and the mice without liver cancers. It was a difference in quality," Lee said.

Since liver tumors caused Tregs to suppress the T cell response against tumors, the researchers tested two drugs to see if they could override the effect of the Tregs. The first was a drug that blocks the T cell checkpoint inhibitor CTLA-4, which unleashes these cells to attack cancer; in the 1990s, Bluestone did pioneering research on CTLA-4 that helped lay the foundations for cancer immunotherapy. The second drug, another anti-CTLA-4 compound, targets Tregs directly and depletes their numbers. Both restored the effectiveness of anti-PD-1 therapy, though the anti-CTLA-4 drug that depletes Tregs was more effective.

The researchers hope to apply this combination therapy in the future to patients whom they know ahead of time are less likely to respond to treatment.

"We’ve never had this kind of precision in immunotherapy in the past," Lee said. "What if, right from the start, you could use a drug that depletes Tregs as a complement to immunotherapy in patients with liver metastasis?"

Authors: Joining Lee and Bluestone, all from UCSF, were Sadaf Mehdizadeh, Jennifer Smith, PhD, Arabella Young, PhD, Ilgiz A. Mufazalov, PhD, Cody Mowery, and Adil Daud, MD.

Funding: In addition to the Parker Institute, support for this research came from an A.P. Giannini Postdoctoral Research Fellowship Award to Lee, and from the National Institutes for Health/NIAID (T32 5T32AI007334-28).

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF’s primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.