PCI Biotech and Immunicum Announce an Extension to Their Research Collaboration to Explore Novel Cancer Vaccination Treatments

On November 30, 2021 PCI Biotech Holding ASA (OSE: PCIB), a cancer focused biopharmaceutical company with a unique intracellular delivery technology via Photochemical Internalisation and Immunicum AB (publ; IMMU.ST), a biopharmaceutical company focused on hard-to-treat established tumors and the prevention of cancer recurrence, reported an extension of their current collaboration (Press release, PCI Biotech, NOV 30, 2021, View Source [SID1234596457]).

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 companies jointly research the possibility to overcome current hurdles in cancer immunotherapy by introducing tumor independent immune targets into the tumor microenvironment, in combination with vaccination or adoptive immunotherapies. The so-called Tumor Independent Antigen concept, which has been invented by Immunicum, could benefit from PCI Biotech’s antigen delivery technologies based on Photochemical Internalisation. Following the encouraging results of the first set of in vitro experiments, during which the delivery protocol of the combination treatment has been optimized, the companies have decided to move ahead to evaluate the novel therapeutic concept in animal models. While the first experiments were conducted by Immunicum, this further in vivo evaluation will be carried out by PCI Biotech.

Commenting on the announcement PCI Biotech’s CEO, Per Walday said: "The results of the initial collaborative experiments are encouraging, supporting the immune response enhancing capability of the fimaVacc platform technology. We are committed to this collaboration and are looking forward to the next series of experiments in animal models, which are aimed to generate data that could pave the way to a potential joint development program."

Erik Manting, CEO of Immunicum added: "At Immunicum, we are continuously studying novel immunotherapy concepts aimed to address hard-to-treat established tumors and to overcome the limitations of currently available cancer therapies. In this collaboration, we are combining our know-how and technology basis with that of PCI Biotech to design potential novel therapeutic concepts and we look forward to advancing the collaboration through in vivo studies as an important next step."

Orion Completes Lead Optimization of its CCR2-Targeted Molecule in Only 6 Months!

On November 30, 2021 Orion Biotechnology, a clinical stage company unlocking the therapeutic potential of G Protein-Coupled Receptors (GPCRs) with a novel drug modality, proven discovery platform and best-in-class molecules, reported the successful completion of its OB-004 lead optimization (Press release, Orion Biotechnology, NOV 30, 2021, View Source [SID1234596387]). OB-004 is a GPCR targeted protein analog of CCL2 that targets the CCR2 receptor. The CCL2/CCR2 pathway plays an important role in oncology, inflammatory, metabolic, and neurological disorders.

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!

Using its proprietary drug discovery technology, Orion successfully completed the development of OB-004 from target identification to lead optimization in only 6 months, a significant reduction in discovery time compared to industry averages. Furthermore, based on inhibition of in vitro signaling, OB-004 is a best-in-class CCR2 antagonist compared to other small molecule CCR2 antagonists in development. This is yet another example demonstrating the superiority of Orion’s discovery platform and novel drug modality to target complex GPCRs.

"Development of a best-in-class CCR2 antagonist in 6 months is an extraordinary accomplishment and validates the power and versatility of our drug discovery platform" said Dr. Oliver Hartley, Vice President of Drug Discovery at Orion Biotechnology. "This powerful tool will allow Orion to rapidly expand its pipeline and also provides us with the opportunity to collaborate with other groups in facilitating the identification and development of GPCR targeted drugs, including the ability to target orphan GPCRs".

Dr. Ian McGowan, Chief Medical Officer at Orion Biotechnology, added "The rapid development of a potent CCR2 antagonist will provide us with the opportunity to evaluate OB-004 in several important diseases with significant unmet medical need including oncological, metabolic, and inflammatory disorders. I look forward to advancing OB-004 into preclinical efficacy studies early next year".

Arrowhead Pharmaceuticals to Participate in Upcoming December 2021 Conferences

On November 30, 2021 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported that it is scheduled to participate in the following upcoming events (Press release, Arrowhead Pharmaceuticals, NOV 30, 2021, View Source [SID1234596346]):

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!

4th Annual Evercore ISI HealthCONx Conference

December 2, 2021, 1:00 p.m. ET – Chris Anzalone, Ph.D., Arrowhead’s president and CEO, will participate in a fireside chat presentation

18th Global Cardiovascular Clinical Trialists Forum

December 3, 2021 – James Hamilton, MD, MBA, Arrowhead’s senior vice president of discovery & translational medicine, will participate in a panel discussion titled, "Developments in Hypertriglyceridemia Trials"

A copy of the presentation materials and/or live webcast links may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.

Chimeric Transforms Portfolio With a Clinically Validated, Off the Shelf, Natural Killer (NK) Cell Platform

On November 30, 2021 Chimeric Therapeutics (ASX:CHM, "Chimeric" or the "Company"), a clinical-stage cell therapy company and the ASX leader in cell therapy, reported that it has entered into an exclusive option to license agreement with Case Western Reserve University (CWRU) for a Clinically validated, Off the shelf, Robust, Enhanced Natural Killer (CORE-NK) cell platform – a platform technology that provides the optimal foundation for the development of multiple next generation NK and CAR-NK products (Press release, Chimeric Therapeutics, NOV 30, 2021, View Source [SID1234596312]).

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!

Natural killer (NK) cells have innate safety features and the natural ability to target and destroy cancer cells through both indirect and direct mechanisms. The challenge with natural killer (NK) cells is that they are not naturally abundant or active enough to overcome cancer.

Dr. David Wald, a leading expert in immuno-oncology at Case Western Reserve University in Ohio, USA designed and developed the CORE-NK platform, enhancing the natural anti-cancer properties of NK cells to be robust and active enough to overcome cancer.

The CORE-NK platform utilizes a foundation of healthy donor NK cells, activating and expanding them to establish an enhanced, off the shelf NK cell platform that can provide an abundant supply of highly active NK cells. Preclinical data on the CORE-NK platform was published in the prestigious family of Nature publications in 2019.

In May 2018 a phase 1 clinical trial was initiated at the Case Comprehensive Cancer Center to study the CORE-NK platform in patients with both solid tumours and blood cancers. The phase 1 clinical trial of the CORE-NK platform was completed in June 2021 with clinical data expected in 2022. The trial examined the safety, bioactivity and efficacy of the CORE-NK platform cells at 3 dose levels in patients with both blood cancers and solid tumours.

With the clinical validation from the phase 1 trial complete, the CORE-NK platform provides the ideal off the shelf platform for the development of next generation NK and CAR-NK products.

Chimeric intends to begin a research collaboration with CWRU to further enhance and engineer the CORE-NK platform cells to develop a next generation CORE-NK platform and three initial CAR-NK products.

"The clinical experience we’ve had with the CORE-NK platform gives us tremendous confidence in the development path for optimized NK and CAR NK products. We look forward to working in close collaboration with Chimeric to bring forward the next generation of NK and CAR NK products to the clinic," said Dr. Wald, MD, PhD, Associate Professor of Pathology Case Western Reserve University School of Medicine and Member, Immune Oncology Program, Case Comprehensive Cancer Center, Associate Director for Basic Research, University Hospitals, Wesley Center for Immunotherapy.

The next generation CORE-NK platform will be developed with enhanced activation and expansion features with plans to study it as a combination therapy in blood cancers.

Three initial CAR-NK products will be developed using the next generation CORE-NK platform as a backbone leveraging Chimeric’s existing pipeline of chimeric antigen receptors (CARs); a CLTX CAR-NK (CHM 1301), a CDH17 CAR-NK (CHM 2301) and a currently undisclosed target CAR-NK (CHM 3301).

Chimeric will also explore additional opportunities to further leverage the CORE-NK platform to develop additional NK and CAR NK products through internal development and/or partnerships with other biotech and pharmaceutical companies.

This strategic agreement is transformative for Chimeric propelling the company forward as the Australian leader in cell therapy and as an emerging global cell therapy company with a robust and advanced portfolio of innovative autologous (personalized) and allogeneic (off the shelf) NK and T cell assets.

"The CORE-NK platform is truly transformative for Chimeric. It provides us with a platform technology that triples our current portfolio by enabling us to accelerate the development of multiple new, off the shelf, NK cell assets that work in perfect synergy with our existing pipeline. We could not be more excited to be bringing the CORE-NK platform into our portfolio and to be working in collaboration with Dr. Wald and the expert team at CWRU. Their clinical trial experience with the CORE-NK platform and their expertise in the development of NK cells will catapult our development forward," said Jennifer Chow, CEO Chimeric Therapeutics.

Under the terms of the option agreement, Chimeric has the exclusive right to license the CORE-NK platform for development and commercialization in cancer. Chimeric intends to rapidly move to complete full licensing of the platform and expects to pay CWRU development milestones and industry standard royalty payments based on commercial net sales. Upfront fees associated with the option agreement will be funded entirely from existing cash reserves.

The area of natural killer cells has seen widespread investment and partnership interest with numerous large transactions involving companies such as Merck, Takeda, Janssen and Kite.

Investor webinar

Chimeric Therapeutics CEO and Managing Director Jennifer Chow will hold an investor webinar today, Wednesday 1 December 2021, at 11am AEDT to elaborate on this announcement and take questions.

Click the link below to register:
View Source

After registering, you will receive a confirmation email about how to join the webinar. A recording of the webinar will be available at the same link shortly after the conclusion of the session.

Molecular Templates Provides Corporate Update and Outlines 2022 Milestones

On November 30, 2021 Molecular Templates, Inc.(Nasdaq: MTEM, "Molecular Templates," or "MTEM" or "the Company"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), reported a corporate update and outlined expected 2022 milestones (Press release, Molecular Templates, NOV 30, 2021, View Source [SID1234596311]).

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!

"2021 was a year of growth for MTEM as we advanced our multiple pipeline programs," said Eric Poma, Ph.D., Chief Executive and Chief Scientific Officer of Molecular Templates. "As we end the year and move into 2022, we look forward to generating further clinical data that builds on the unique biology we are seeing from three ongoing studies with MT-6402, MT-5111, and MT-0169. We expect to file an IND in 2H22 for our CTLA-4 program and will continue to advance our earlier stage pipeline with ETBs in preclinical development targeting TIGIT, TROP-2, and SLAMF7."

2021 Accomplishments, Status Updates, and Expected 2022 Milestones

MT-6402 (PD-L1 ETB with Antigen Seeding)

MT-6402 is the first of the Company’s 3rd-generation ETBs to enter the clinic. It targets PD-L1 and incorporates the Company’s antigen seeding technology. MT-6402 was designed to directly destroy PD-L1+ tumor cells and alter the immunosuppressive tumor microenvironment through direct cell-kill of PD-L1+ immune cells. In addition, antigen seeding allows MT-6402 to induce the presentation of an MHC class I CMV antigen on tumor cells for pre-existing CD8 T-cell recognition and destruction in HLA-A2+ CMV+ patients. A Phase I study in relapsed/refractory patients with PD-L1-expressing tumors and/or immune cells in the tumor microenvironment was initiated in 2H21 at a starting dose of 16 mcg/kg. Highlights from the on-going Phase I study include:

4 patients have been treated (2 NSCLC, 1 melanoma, 1 ovarian) with no dose limiting toxicities (DLTs) to date
1 patient with stable disease (SD) at 5+ months with reduction in non-measurable bone metastasis
3 patients with progressive disease
Target-mediated, HLA type-independent pharmacodynamic effects after MT-6402 treatment observed in majority of patients including peripheral CD14+ monocyte depletion
One patient had monocyte depletion of >95% that was achieved in cycle 2 and is maintained and on-going at 5+ months of treatment, demonstrating potential for sustained effect with repeat dosing
One patient had monocyte depletion of 90% that was achieved in cycle 2 and sustained through two cycles of therapy before the patient discontinued the study for disease progression at the end of cycle 2
One patient had monocyte depletion of ~21% but discontinued at the end of cycle 1 for disease progression
One patient had no evidence of monocyte depletion but discontinued after 10 days on therapy for disease progression and did not complete cycle 1
Similar depletion was not observed in non-PD-L1-expressing cells (i.e., NK cells, B-cells, etc) nor was monocyte depletion noted in patients treated with other ETBs (MT-3724, MT-0169, or MT-5111)
Significant increases in key cytokines including IL- 2 and activated CD8+ T-cell markers including CD69 noted in patients
Comparable immune subset and/or cytokine changes not seen with approved PD-L1 agents
One HLA-A2 CMV+ patient (i.e., antigen-seeding eligible patient) has been treated to date
Patient is a NSCLC chemotherapy-ineligible patient whose disease had progressed following treatment with a combination of checkpoint inhibitors (ipilimumab and nivolumab); patient has non-measurable bone disease
On-going monocyte depletion of >95% observed at 5+ months of dosing
Initial increase of ~ 50% in CMV antigen-specific T-cells after dosing with MT-6402 with subsequent near-complete extravasation of CMV antigen-specific T-cells from the periphery despite a general increase in total peripheral CD8+ effector T-cells (effect not seen in non-HLA-A2 CMV-negative patients)
Multiple sites of bone disease had resolved on bone scan with only one remaining site which showed decreased uptake
Dose escalation continues as planned
In November, MT-6402 was granted Fast Track Designation for the treatment of patients with advanced NSCLC expressing PD-L1
"We are excited to see pharmacodynamic effects with MT-6402 this early in dose escalation in the Phase I study. No approved checkpoint agent has shown an ability to alter immune subset composition or induce cytokine changes in a PD-L1-targeted fashion," said Roger Waltzman, MD, Chief Medical Officer of Molecular Templates. "We believe that the actual clearance of PD-L1+ immune cells and not merely the steric inhibition of PD-L1 on immune cells may work to more potently alleviate tumor-mediated immunosuppression by removing immunosuppressive myeloid cells acting as a barrier to immunotherapy. Additionally, we are seeing early evidence supporting our unique antigen seeding approach to alter tumor immunophenotype. We are excited to see this unique biology potentially driving patient benefit and believe these data support both monotherapy treatment in relapsed/refractory patients as well as future combination studies in earlier lines of therapy with PD-1 antibodies or other therapies."

MT-5111 (HER2 ETB)

MT-5111 is the Company’s 2nd-generation ETB targeting HER2. It is designed to avoid competition with and to overcome the primary mechanisms of tumor resistance to current therapies that target HER2. MT-5111 destroys HER2-positive tumor cells through a novel mechanism of action (enzymatic ribosomal destruction), targeting HER2 via a distinct epitope from trastuzumab and pertuzumab, and improving tumor penetration with a smaller size compared to HER2 antibodies (55 kDa vs 146 kDa). Dose escalation is on-going in the Phase I study with dose levels now at drug concentrations that are predicted to be active in metastatic breast cancer. Dose escalation will continue in solid tumor HER2-positive patients, and an expansion cohort in patients with metastatic breast cancer was initiated in 4Q21. Highlights from the on-going Phase I include:

27 patients have been treated to date with MT-5111 across 7 dose escalation cohorts ranging from 0.5 mcg/kg to 10 mcg/kg without any DLT’s
MT-5111 has been well-tolerated with no significant immuno- or cardiotoxicity observed
The expansion cohort for patients with metastatic breast cancer is open for enrollment
Dosing in the cohort is at 10 mcg/kg with the potential for dose-escalation
Dose levels of 10 mcg/kg or higher are expected to be required to achieve drug concentration levels that could drive efficacy in breast cancer
"We believe we are now at dose levels in the Phase I study that should be in the therapeutic range for MT-5111, and, with the opening of the breast cancer cohort, we are assessing the activity in the patient population we believe is most likely to respond," said Dr. Roger Waltzman. "We believe the tolerability to date supports further dose escalation."


MT-0169 is the Company’s 2nd-generation ETB targeting the CD38 receptor, found on the surface of multiple myeloma and non-Hodgkin lymphoma (NHL) cells. MT-0169 was designed to destroy CD38+ tumor cells through induced internalization of CD38 and cell destruction through a novel mechanism of action (enzymatic ribosomal destruction). MT-0169 is the most potent ETB developed to date and the study initiated with the highest starting dose for any ETB. Relevant pharmacodynamic data from patients treated in the first dose cohort show NK cell depletion consistent with maximal levels achieved with CD38 antibody therapy. MTEM assumed full rights to MT-0169 in August 2021 and is opening new sites for the Phase I study. As part of a protocol amendment, CD38+ NHL patients will be dosed in addition to myeloma patients. Highlights from the on-going phase I include:

5 multiple myeloma patients have been treated to date
No serious adverse events (SAEs) have been observed. Two cardiac adverse events were observed that meet criteria for DLT. Both evaluations were triggered by asymptomatic elevations in high-sensitivity troponin values. As previously disclosed, the first DLT was an asymptomatic, rapidly reversible episode of myocarditis that did not require treatment. The second DLT occurred recently and is an asymptomatic, nonischemic cardiomyopathy. We believe both DLTs may be due to activity against low CD38-expressing cells in the cardiac endothelium. We have not seen evidence of any clinically relevant cardiac adverse event such as myocarditis or cardiomyopathy in any other ETB program (MT-3724, MT-5111, MT-6402) at any dose.
Clearance of CD38+ NK cells noted in all patients with maximal levels of depletion occurring within 24 hours and consistent with maximal depletion seen with CD38 antibodies
Rapidity and depth of CD38+ NK cell-kill is substantially higher in humans than what was seen in non-human primate studies
One patient has shown symptomatic benefit with a reduction in myeloma-induced bone pain
A revised protocol will be submitted to explore dose reduction with MT-0169 to reduce the risk of toxicity caused by the destruction of low CD38-expressing cells and enable patients to continue MT-0169 therapy for a duration that may drive tumor benefit
"MT-0169 has shown potent and rapid pharmacodynamic activity against CD38+ NK cells with early signs of clinical benefit," said Dr. Roger Waltzman. "The pharmacodynamic activity of NK cell-kill at 50 mcg/kg exceeded what was expected based on the non-human primate data and is consistent with maximal achievable levels. In general, we have observed that MT-3724, MT-6402, and MT-0169 have all shown substantially more pharmacodynamic activity in patients compared to what was seen in NHPs at equivalent or higher doses. We will be exploring lower doses in the proposed revised protocol and expect to report additional data in 2022."

Preclinical Pipeline

MTEM continues to advance its pipeline with its CTLA-4 and TIGIT ETBs representing novel approaches to key immune-oncology targets and its TROP2 and SLAMF7 ETBs applying unique biology to validated targets. MTEM also continues to expand the capabilities of the ETB technology.

IND filing of CTLA-4 program expected in 2H22
Lead selection for TIGIT, TROP-2 with antigen seeding, and SLAMF-7 is ongoing
Additional target selection and scaffold improvements expected in 2022
"We continue to move forward with programs against new targets using the unique biology of ETBs, and we continue to advance the biology of the ETB scaffold," continued Dr. Poma. "We believe MT-6402 and our CTLA-4 and TIGIT programs represent a new way of altering the immune environment in patients with cancer through targeting and destroying myeloid-derived suppressor cells and regulatory T cells (Tregs). Additionally, we believe that new mechanisms of action against validated targets like TROP-2 and SLAMF-7 are needed in these diseases with high unmet medical need."

Key Milestones for 2022

"We believe that 2022 will be another exciting year for the Company with potentially transformational data across our three ongoing clinical programs, an IND filing expected for our CTLA-4 ETB and continued preclinical development," concluded Dr. Poma. "We have substantial cash reserves into 4Q23 to drive development of a broad range of compounds at MTEM."

Continued data read-outs on all three clinical programs
IND filing for ETB targeting CTLA-4
Advancement of ETBs targeting TROP2, TIGIT, SLAMF-7
The Company has cash runway into 4Q23
Participation in Evercore ISI 4th Annual HealthCONx

The Company will participate in a fireside chat and hold 1-on-1 investor meetings at the Evercore ISI 4th Annual HealthCONx, to take place November 30 – December 2, 2021.