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Gliknik Inc. Raises $11.5 Million in Series C Financing

On June 24, 2021 Gliknik Inc., an immunology company dedicated to patients with cancer and autoimmune disorders, reported that it has successfully completed an $11.5 million Series C Preferred Stock financing (Press release, Gliknik, JUN 24, 2021, View Source [SID1234584333]). First In Ventures (FIV) led the Series C with SAISO Partners and affiliates of RDA Ventures and Garden Street Holdings also participating. The proceeds are targeted to progress the growing pipeline of Gliknik product candidates. Gliknik has secured $81 million to date to advance its programs.

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"We believe that Gliknik has created several potential best-in-class mid-stage assets," said Scott Roth, managing partner of FIV. "This capital will help unlock the potential of these compounds and uniquely positions Gliknik to make a difference for patients with cancer or autoimmune disorders."

Funding will help advance Gliknik clinical and pre-clinical programs, including:

A randomized double-blind, placebo-controlled phase 2 study of Gliknik immuno-oncology compound biropepimut-S, which is nearing completion. Clinicians are assessing two-year endpoints in the prevention-of-recurrence of high-risk squamous cell oral cavity cancer.
Gliknik immune modulating compound GL-2045, a recombinant mimetic of pooled human IVIG, which is a potent clinical candidate under active development by Gliknik licensee Pfizer for autoimmune diseases. Gliknik believes that based on potency, purity and anticipated convenience, GL-2045 has the potential to be a disruptive advance for autoimmune diseases that could help address the current critical shortage of IVIG.
GL-0719 is a new type of complement modulator, which is designed to control diseases while leaving critical host defense systems intact. GL-0719 is poised to enter a phase 1 trial in 2021.
Other compounds in preclinical development
Kyle Rusconi, a founder of FIV, is joining the Gliknik Board. "During the last several years, Gliknik has created a significant pipeline of important compounds," said Mr. Rusconi. "This scientific development was done in a capital-efficient manner that preserved shareholder equity."

"We are humbled by the depth of support from our investor base and welcome the addition of discerning investors with a long-term view," said Gliknik CEO David Block.

Foundation Medicine Collaborates on Research Published in The New England Journal of Medicine That Identifies Resistance to KRAS Inhibitors and Underscores Need for Novel Therapeutic Strategies

On June 24, 2021 Foundation Medicine, Inc. and its collaborators reported results from a Dana-Farber Cancer Institute-led study that used genomic testing, including Foundation Medicine’s liquid-based comprehensive genomic profiling (CGP) test, FoundationOneLiquid CDx, among several assays, to investigate resistance mechanisms in 38 patients with cancer treated with a KRAS G12C inhibitor (Press release, Foundation Medicine, JUN 24, 2021, View Source [SID1234584332]). The study found a complex landscape of acquired resistance mechanisms, with putative resistance mechanisms identified in 45% of patients. These mechanisms were diverse, and some patients (18%) had multiple resistance alterations. Study findings support the need for development of additional KRAS inhibitors and combination treatment strategies and reinforce the utility of liquid biopsy assays in evaluating resistance. The study, "Acquired Resistance to KRAS G12C Inhibition in Cancer," was published yesterday in The New England Journal of Medicine.

The KRAS oncogene encodes a protein frequently altered in cancer, and mutations typically occur at hotspots in the protein, increasing the activity of KRAS and driving pro-tumorigenic signaling. Although KRAS mutations are among the most common cancer drivers, only recently have investigational KRAS inhibitors entered clinical development, with the first KRAS inhibitor just approved for certain patients with lung cancer. In this study of patients receiving an investigational therapy, researchers identified multiple resistance pathways – in some cases even within a single sample – through the use of genomic testing from several labs. These findings help researchers better understand the landscape of acquired resistance to KRAS inhibitors to inform the development of additional therapeutics targeting KRAS alterations or combination therapies designed to block oncogenic signaling and result in clinical responses.

"Resistance mechanisms to cancer treatment are often complex, which is challenging for oncologists and researchers to describe and effectively counter. That’s why we were excited to help incorporate genomic testing though Foundation Medicine’s comprehensive liquid biopsy assay into this study – one of the first analyzing resistance mechanisms to KRAS inhibitors," said Alexa Schrock, Ph.D., Director, Clinical Development at Foundation Medicine. "Comprehensive liquid biopsy assays not only enable widespread access to genomic testing, which is particularly appealing to patients with treatment resistance, but they also provide insights to help drive the development of new therapeutic approaches for these patients."

The study included a total of 38 patients, 27 with non-small cell lung cancer (NSCLC), 10 with colorectal cancer and one with appendiceal cancer. Using multiple genomic tests, mechanisms of putative resistance to adagrasib monotherapy were detected in 17 patients (45% of the cohort), eight of whom had multiple resistance mechanisms. In one patient with NSCLC (tested with FoundationOne Liquid CDx), testing revealed acquired KRAS alterations including H95D, R68S, G12W and G12V, as well as acquired RTK and MAPK pathway alterations.

This clinical analysis was aided by a deep mutational scanning screen of a library of KRAS G12C variants that systematically defined potential secondary alterations conferring resistance to KRAS G12C inhibition. The findings suggest a diverse landscape of KRAS G12C inhibitor resistance mechanisms, which can help inform novel therapeutic strategies to effectively overcome this drug resistance in patients with cancer.

About FoundationOneLiquid CDx

FoundationOne Liquid CDx is a qualitative next generation sequencing based in vitro diagnostic test for prescription use only that uses targeted high throughput hybridization-based capture technology to analyze 324 genes utilizing circulating cell-free DNA (cfDNA) isolated from plasma derived from anti-coagulated peripheral whole blood of advanced cancer patients. The test is FDA-approved to report short variants in over 300 genes and is a companion diagnostic to identify patients who may benefit from treatment with specific therapies (listed in Table 1 of the Intended Use) in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Patients who are negative for companion diagnostic mutations should be reflexed to tumor tissue testing and mutation status confirmed using an FDA-approved tumor tissue test, if feasible. For the complete label, including companion diagnostic indications and complete risk information, please visit www.F1LCDxLabel.com.

Huntsman Cancer Institute Begins Treatment with Mevion Compact Proton Therapy System

On June 24, 2021 Mevion Medical Systems reported that the first proton center in the Mountain West, the Senator Orrin G. Hatch Center for Proton Therapy, has opened at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) and began treating patients on May 11th with the MEVION S250i Proton Therapy System (Press release, Mevion Medical Systems, JUN 24, 2021, View Source [SID1234584331]). Despite the challenges of the COVID-19 pandemic, the Mevion team successfully installed the MEVION S250i in 7 months from the delivery of the accelerator.

HCI is the only National Cancer Institute-designated Comprehensive Cancer Center in the Mountain West and serves a geographic region that includes all of Utah, Idaho, Montana, Nevada, and Wyoming.

"After more than a decade of monitoring and evaluating the evolution of proton therapy technology, along with the needs of our patients, we are excited to officially launch our proton center and to provide this extraordinary treatment option to our patients," said Bill Salter, Ph.D., Senior Director of Radiation Oncology at HCI and Professor and Chief of the Division of Medical Physics at the U of U. "Our initial experience of treating both adult and pediatric tumors has already made evident the unique clinical capabilities of proton technology."

The center features Mevion’s industry leading HYPERSCAN pencil beam scanning technology and Adaptive Aperture pMLC. The powerful duo provides faster and more precise dose delivery and minimizes damage to surrounding healthy tissue and sensitive organs at risk. HCI has also integrated a diagnostic CT on-rail system and a surface-guidance tracking system, enabling a state-of-art Image-Guided Proton Therapy (IGPT) configuration to align and treat patients with the upmost accuracy.

Thanks to the reduced size and complexity of the MEVION S250i, the HCI Center for Proton Therapy was placed in a small available space alongside HCI’s existing radiation therapy department. This significantly decreased the project construction and operation cost and allows the cancer center to share existing resources and give patients access to all of HCI’s cancer treatment and research offerings under one roof.

"It is to our greatest pleasure that the underserved patients in the Mountain West now have access to proton therapy," said Tina Yu, Ph.D., chief executive officer of Mevion Medical Systems. "We are honored to partner with HCI to make this happen and look forward to our many years of collaboration and research to further advance this superior treatment modality."

As the leading supplier of compact proton therapy systems in the United States, Mevion has been selected by more leading cancer centers, including NCI-Designated Cancer Centers, and has treated over 6,000 patients worldwide.

Transgene: First Patient Enrolled in Expanded Phase II Clinical Trial of TG4001 + Avelumab Vs Avelumab Alone in Patients With HPV16-positive Anogenital Cancers

On June 24, 2021 Transgene (Paris:TNG) (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, reported that a first patient has been enrolled in a randomized, controlled Phase II study evaluating the combination of TG4001 with avelumab versus avelumab monotherapy in patients with HPV16-positive anogenital tumors (NCT: 03260023) (Press release, Transgene, JUN 24, 2021, View Source [SID1234584330]).

TG4001 IS AN INVESTIGATIONAL THERAPEUTIC VACCINE TARGETING HPV-POSITIVE TUMORS, including cervical, anal, and other anogenital cancers. It is based on a Vaccinia vector (MVA), which is engineered to express HPV16 E6 and E7 antigens and interleukin 2 (IL-2). TG4001 is designed to alert the immune system specifically to cells presenting these HPV antigens (that can be found on HPV-related tumors) and to induce a specific cellular immune response against these cancer cells.

Based on promising data obtained in the Phase Ib/II part of the trial, Transgene is progressing the development of TG4001 in combination with avelumab, through a randomized Phase II trial and an extended collaboration with the alliance of Merck KGaA, Darmstadt, Germany, and Pfizer, which is supplying avelumab.

PHASE II TRIAL AIMS TO SHOW THE SUPERIORITY OF TG4001 + AVELUMAB OVER AVELUMAB MONOTHERAPY

The randomized Phase II trial is focusing on patients with recurrent or metastatic HPV16-positive anogenital cancer, including cervical, vulvar, vaginal, penile, and anal cancer, without liver metastases. In the Phase Ib/II part of the study, very encouraging clinical outcome was observed in patients without liver metastases [1,2].

Patients will be randomized to either receive the combination regimen of the therapeutic vaccine TG4001 and avelumab or avelumab alone. The trial will be enrolling patients in the USA and in Europe (France and Spain).

The primary endpoint of the trial is progression-free survival (PFS) according to RECIST 1.1. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS) and a series of immunological parameters.

An interim analysis will be performed after the enrollment of approximately 50 patients. Transgene expects to communicate interim analysis data around the end of 2022.

Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene, added: "We are confident that the combination regimen of TG4001 and avelumab has the potential to deliver improved progression-free survival for patients with advanced/recurrent HPV16-positive anogenital cancer without liver metastases. This confidence is based on the very encouraging results from the initial Phase Ib/II study, which showed important clinical benefits in this patient population in terms of response rate and progression-free survival. This earlier study part also showed that patients had vaccine-induced reactive T cells against E6, E7 or both. This randomized trial has been designed to further demonstrate that the addition of TG4001 to an immune checkpoint inhibitor can improve the clinical outcome for patients with HPV16-positive anogenital cancer without liver metastases. We are looking forward to announcing the interim results from this expanded study which could be a key milestone in bringing TG4001 to patients in need of improved treatment options."

About the trial
The multi-center, open label, randomized Phase II trial (NCT03260023) is designed to compare the efficacy of the combination of TG4001 and avelumab versus avelumab alone in patients with HPV16-positive anogenital cancers who have disease progression after a maximum of one line of systemic treatment for recurrent/metastatic disease, or who are not eligible for first-line chemotherapy.

Prof. Christophe Le Tourneau, M.D., PhD, Head of the Department of Drug Development and Innovation (D3i) at the Curie Institute, is the Principal Investigator of the study. The trial is being conducted in collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer Inc. (NYSE: PFE), which are providing avelumab for the trial. Avelumab is co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer Inc. Transgene will continue to be the sponsor of the trial and conduct the trial.

Patients will receive TG4001 at the dose of 5×107 plaque-forming units (pfu), subcutaneously (SC), weekly for 6 weeks, every 2 weeks up to six months, and every 12 weeks thereafter, in combination with avelumab or avelumab alone at 800 mg, intravenously (IV) every two weeks, until disease progression. The primary endpoint of the trial is progression-free survival (PFS) according to RECIST 1.1. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS) and other immunological parameters. The trial could enroll approximately 150 patients until the final analysis.

Patients with liver metastases will be followed in an ancillary arm and will not be included in the primary analyses.

***

About the data presented at SITC (Free SITC Whitepaper) 2020 and ESMO (Free ESMO Whitepaper) IO 2020 [1,2]
The results from the Phase Ib/II parts of the trial combining TG4001 with avelumab in HPV16-positive recurrent and/or metastatic malignancies were presented at SITC (Free SITC Whitepaper) 2020 [1] and ESMO (Free ESMO Whitepaper) IO 2020[2].

The combination of TG4001 and avelumab demonstrated anti-tumor activity (23.5% ORR) in patients with previously treated recurrent and/or metastatic HPV-related cancers (including patients with oropharyngeal cancers and anogenital cancers). Presence of liver metastases had a profound impact on the outcome in terms of ORR and PFS. In patients without liver metastases, an ORR of 34.8% and a median PFS of 5.6 months were achieved. The treatment induced HPV-specific T-cell responses and was associated with increased levels of immune cell infiltration in the tumors and expression of genes associated with activation of the immune system.

About TG4001
TG4001 is an investigational therapeutic vaccine based on a non-propagative, highly attenuated Vaccinia vector (MVA), which is engineered to express HPV16 antigens (E6 & E7) and an adjuvant (IL-2). TG4001 is designed to have a two-pronged antiviral approach: to alert the immune system specifically to cells presenting the HPV16 E6 and E7 antigens, that can be found in HPV16-related tumors, and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2). TG4001 has been administered to more than 300 individuals, demonstrating good safety and promising efficacy results [1, 2]. Its mechanism of action and good safety profile make TG4001 an excellent candidate for combinations with other therapies in HPV-mediated solid tumors.

PharmaCyte Biotech Provides Update on Status of Activities to Lift Clinical Hold

On June 24, 2021 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box , reported the efforts being undertaken by the Company to have the U.S. Food and Drug Administration (FDA) clinical hold lifted (Press release, PharmaCyte Biotech, JUN 24, 2021, View Source [SID1234584329]). These efforts are necessary so that PharmaCyte may proceed with its planned clinical trial in locally advanced, inoperable, pancreatic cancer (LAPC).

The Company’s Chief Executive Officer, Kenneth L. Waggoner, discussed the background of the clinical hold stating, "On September 1, 2020, the Company submitted an Investigational New Drug Application (IND) to the FDA for our planned Phase 2b clinical trial in LAPC. On October 1, 2020, the Company received notice from the FDA that it had placed our IND on clinical hold. And on October 30, 2020, the FDA sent a letter to us setting forth the reasons for the clinical hold and specific guidance on what we must do to have the clinical hold lifted."

For the purpose of addressing the clinical hold, the Company has assembled a team of regulatory and scientific experts to respond to the items requested by the FDA. That team has been actively working to complete the list of items requested by the FDA. Those items can be found on pages 28 and 29 of PharmaCyte’s latest Form 10-Q for the period ending January 31, 2021.

Mr. Waggoner then explained, "The Company is in varying stages of addressing the studies and acquiring the information requested by the FDA to have the clinical hold lifted. Thus far:

The Company has successfully completed a 3, 6, 9, and 12-month product stability study on the Company’s clinical trial product (CypCaps), including container closure integrity testing for certain timepoints; the next time point in this ongoing study will be at 18 months of product stability.
The Company has designed and commenced various additional studies recommended by the FDA, including a stability study on the cells from the Master Cell Bank (MCB) used to make the CypCaps, which are already at the 3-year stability timepoint, and further sequence analysis of the DNA encoding of the Cyp2B1 gene in the encapsulated cells in the CypCaps. It has also collated existing information on the reproducibility and quality of the filling of the MCB cells into vials ready for CypCaps manufacturing as requested by the FDA.
The Company has designed and commenced biocompatibility studies such as (i) a Subchronic and Chronic Toxicity study; (ii) a Skin Sensitization study; (iii) an Acute Systematic Toxicity study; (iv) an Ames test [Genotoxicity Bacteria and Reverse Mutation tests]; (v) an Intracutaneous test; (vi) a Complement Activation test; (vii) a Hemolysis test; (viii) an In Vitro Cytotoxicity test; and (ix) an In Vivo Micronucleus assay. To enable these tests to be performed, the Company has already manufactured and delivered an additional 400 syringes of empty capsules. Some of the data being generated will also be used to demonstrate comparability with the CypCaps successfully used—in two earlier German clinical trials for pancreatic cancer.
The Company has designed and commenced studies designed to show that CypCaps are not in any way adversely affected by the catheters used by interventional radiologists to deliver them, nor by the contract media used to visualize the blood vessels during implantation of the CypCaps. Further, the studies are designed to demonstrate how robust the CypCaps are during delivery and use as well as to document that the syringes used to deliver the CypCaps will allow delivery consistently, smoothly and safely.
Austrianova is providing additional detailed confidential information to the FDA on the manufacturing process, including information on the improvements made to the product since the last clinical trials with respect to reproducibility and safety, but that have not changed the overall physical characteristics of the CypCaps. The Company is supporting Austrianova in this work.
The Company is in the process of updating its documentation to include (i) more pre-clinical data as discussed above, (ii) some additional parameters for release of the CypCaps, (iii) specifically recommending the catheters and contrast used to deliver the CypCaps as well as (iv) extending its discussion on immunology.
Finally, the Company has designed an abbreviated study in pigs to address biocompatibility and long-term implantation of the capsules. This animal study will complement the positive data already available from the previous human clinical trials showing the safety of CypCaps implantation for up to two years in humans.
The Company feels that the carcinogenicity data obtained to date, together with the long-term data from the two previous German trials, show that CypCaps are unlikely to cause any long-term cancer. Furthermore, the patients who will be treated with CypCaps are already suffering with inoperable, late-stage pancreatic cancer, and chemotherapeutics, like ifosfamide, (the drug given at low concentrations with the CypCaps), are approved for treatment of cancer even through it is known to have a carcinogenic potential. Indeed, virtually all anti-cancer treatments used today by their very nature have an inherent potential to cause cancer. Moreover, the cells within the CypCaps are primed by ifosfamide to commit cell suicide if they try to divide."
Mr. Waggoner continued, "The list of items that we have been addressing is lengthy, time consuming and costly. Some of the studies required by the FDA caused us to find suitable partners and Contract Research Organizations to assist us in the work. But our team has been working tirelessly on every item and will continue to do so until we have done all that we can to satisfy the FDA requests. In addition, we plan to request a meeting with the FDA for further guidance and to update them on the progress that we have made.

"As we continue to reach milestones on the requested studies, we will strive to report on the material developments that we believe will allow us to get the clinical hold lifted."

To learn more about PharmaCyte’s pancreatic cancer therapy and how it works inside the body to treat locally advanced inoperable pancreatic cancer, we encourage you to watch PharmaCyte’s documentary video complete with medical animations at: View Source