On June 23, 2020 RubrYc Therapeutics, Inc., a pre-clinical biotherapeutics company developing epitope selective therapies to improve outcomes for cancer and serious autoimmune disease patients, reported the presentation of discovery and pre-clinical data from their lead program RTX-003, a CD25 targeted monoclonal antibody for selective depletion of regulatory T cells (Tregs) in the tumor microenvironment (TME) (Press release, RubrYc Therapeutics, JUN 23, 2020, View Source [SID1234561412]).

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A poster titled "Discovery of Epitope-Selective Anti-CD25 Targeting Therapeutic Antibodies for Effective Treg Cell Depletion in Cancer using a Machine Learning-Based Platform" will be presented by Dr. Phung Gip, Director of Biology, at the AACR (Free AACR Whitepaper) Virtual Conference on June 22nd (Abstract #6055).

RubrYc’s technology addresses one key limitation in early antibody discovery, which is immunodominance – an evolutionary bias toward specific epitopes that steer antibody selection away from potentially high-efficacy epitopes. An integrated computational and laboratory approach to antibody discovery enables us to build focused epitope embodiments of structural epitopes. These epitope embodiments, called Meso-scale Engineered Molecules (MEMs), are used in antibody selections to steer hits towards the intended epitopes. In our lead program RTX-003, we target CD25 (IL2Rα) which is highly expressed on regulatory T-cells (Tregs) that drive immunosuppression in the TME. Depletion of Tregs can restore anti-tumor T effector (Teff) function in the TME by increasing the Teff/Treg ratio, especially when combined with checkpoint-inhibitors. Using our epitope-selective antibody discovery platform, we built MEMs that embody eight CD25 structural epitopes outside the CD25:IL-2 interface. Through both immunization and in vitro selection based approaches, several medium to high-affinity (median KD = 25 nM) anti-CD25 antibodies from each of the eight intended CD25 epitopes were identified and confirmed to be on prescribed epitope by cross-blocking assays and in-epitope alanine mutations. Several conventional- and epitope-selective anti-CD25 clones were converted to human IgG1 and tested in in vitro assays. As a result, these antibodies bound specifically to CD25+ cells, preserve IL-2 signaling via pSTAT5 assays and elicited potent ADCC activity using human effector cells, and had in vivo efficacy superior to benchmark antibodies. These studies demonstrate that our integrated computational and laboratory platform improves the productivity of epitope-selective antibody discovery and produces clones with improved biological function and therapeutic potential.

Dr. Isaac Bright, CEO, said, "The in vivo results from our lead program RTX-003, are the first demonstration that RubrYc Discovery Engine can yield highly epitope-specific monoclonal antibodies with enhanced biological function. These mAbs can be used for internal or partnered programs in monospecific and bispecific antibodies, antibody drug conjugates or cellular therapies. We look forward to refining the platform and bolstering our development capabilities for accelerated discovery and development of epitope-specific therapeutics for patients in need."

On June 23, 2020 Kadmon Holdings, Inc. (NYSE:KDMN) reported that the first patient has been dosed in a Phase 1 clinical trial evaluating KD033, an anti-PD-L1/IL-15 fusion protein, in patients with metastatic or locally advanced solid tumors (Press release, Kadmon, JUN 23, 2020, View Source [SID1234561410]). KD033 is a novel immunotherapy designed to stimulate innate and adaptive immune responses directed to the tumor microenvironment.

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"We are pleased to initiate clinical development of KD033, which has demonstrated encouraging efficacy and durability in a variety of tumor types in preclinical models," said Harlan W. Waksal, M.D., President and CEO of Kadmon. "By directing the anti-tumor activity of IL-15 to the tumor microenvironment, KD033 has the potential to stimulate patients’ immune responses to fight cancer while avoiding systemic toxicities. This study initiation represents an important milestone for Kadmon and our platform of IL-15-containing fusion proteins. We look forward to providing further updates on this trial as they become available."

Recombinant IL-15 (rIL-15) is an immunostimulatory cytokine that has demonstrated clinical activity in the treatment of several cancers. rIL-15 expands key tumor-fighting cell types, including natural killer (NK), natural killer T (NKT) cells and memory T cells, without expanding immunosuppressive Treg cells, allowing for robust and durable anti-tumor responses. Clinical use of rIL-15 has been limited by its short half-life and narrow therapeutic window. To address these challenges, Kadmon has developed KD033, which is designed to direct IL-15 activity to the tumor microenvironment of PD-L1-expressing tumors and to achieve a greater therapeutic window. KD033 is designed to promote long-lasting efficacy while reducing systemic exposure of IL-15 to potentially increase safety and tolerability.

In preclinical studies, a single dose of KD033 demonstrated robust in vivo pharmacological activity and inhibited tumor growth across multiple syngeneic mouse models. KD033 also induced T-cell memory, resulting in mice that remained tumor-free following several tumor re-challenges. KD033 demonstrated significant tumor inhibition in animal models that are resistant to approved immunotherapies such as PD-L1, PD-1 or CTLA-4 antibodies.

About the KD033-101 Clinical Trial

KD033-101 is a Phase 1, open-label, dose-escalation and dose-expansion study investigating the safety and efficacy of KD033 in patients with metastatic or locally advanced solid tumors. The dose-escalation phase of the study will evaluate the pharmacokinetics and pharmacodynamics and identify the maximum tolerated dose (MTD) of KD033. The dose-expansion phase of the study will enroll approximately 15 patients who have progressed or are refractory to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy to assess safety, efficacy and determine the recommended Phase 2 dose (RP2D) of KD033.

About KD033

KD033 is a novel immunotherapy developed in-house and is fully owned by Kadmon. KD033 combines an anti-PD-L1 antibody with IL-15, a cytokine that expands key tumor-fighting cell types, including natural killer (NK), natural killer T (NKT) and memory T cells, to potentially induce durable responses and inhibit tumor growth. The anti-PD-L1 antibody directs IL-15 activity to the tumor microenvironment, limiting systemic exposure of IL-15 to potentially increase safety and tolerability. KD033 was well tolerated in GLP toxicology studies at clinically relevant doses. KD033 process development and manufacturing was completed through a successful collaboration with Wuxi Biologics and exhibited desired manufacturability and stability criteria.

KD033 is the most advanced candidate from Kadmon’s IL-15 fusion protein platform. The Company is developing a portfolio of therapies combining IL-15 with select antibodies for the treatment of cancer.

On June 23, 2020 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 that it is closing the gap in completing its Investigational New Drug application (IND) for its planned clinical trial in locally advanced, inoperable, pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, JUN 23, 2020, View Source [SID1234561409]).

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PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, stated, "We are pleased to report that the major challenges we faced in completing the IND have now been overcome. The remaining work no longer involves research and development or manufacturing. The remaining work now resides with our consultants to complete the documents required for the IND submission."

The Stability Study tests, which include the Container Closure Integrity test, are underway. These are the tests for the first "time point" in the two-year Stability Study. Successful data from these tests are required by the U.S. Food and Drug Administration (FDA) and will be incorporated into the IND.

Most of the remaining work is being handled by PharmaCyte’s consultants. Set forth below is a list of the major items to be finalized by PharmaCyte and its consultants before PharmaCyte submits the IND to the FDA.

Trial Protocol
Investigator’s Brochure
Environmental Analysis
General Investigation Plan
Introduction Summary
Nonclinical Overview
Clinical Overview
Nonclinical Written and Tabulated Summaries
Drug Master File
Pharmacy Manual
Informed Consent
Study Reports and related information of prior clinical studies pertinent to LAPC
Regulatory Publishing of the IND and supporting documents
While this is not a complete list of all of the remaining tasks, it identifies the critical ones. However, there are no further pre-clinical tests remaining to commence before submitting the IND to the FDA.

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

On June 23, 2020 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company committed to giving patients back their innate ability to fight cancer, reported financial results for the first quarter 2020 and provided an update on clinical and corporate progress (Press release, Affimed, JUN 23, 2020, View Source [SID1234561408]).

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"We continue to move our clinical programs forward in close collaboration with our investigators and partners," said Dr. Adi Hoess, CEO of Affimed. "We have strengthened the management team with the recent hiring of Angus Smith as CFO, which nicely complements the additions of Dr. Andreas Harstrick as CMO and Dr. Arndt Schottelius as CSO earlier in the year. With good progress in our clinical programs, the pre-clinical pipeline and the completion of the management team, we are well positioned to increase our leadership position as innovators of innate immune system-based therapeutics."

Development Program Updates
AFM13 (CD30/CD16A)

Affimed has successfully activated 46 clinical study sites in nine countries in the on-going Phase 2 registration-directed study of AFM13 as monotherapy in relapsed or refractory patients with CD30-positive peripheral T-cell lymphoma (pTCL).
The investigator-sponsored Phase 1 study with the University of Texas, MD Anderson Cancer Center to investigate the combination of AFM13 with allogeneic NK cells in CD30+ Lymphomas has completed the required validation work in order to administer a stable complex of AFM13 pre-mixed with cord blood-derived allogeneic NK cells.
AFM24 (EGFR/CD16A)

After the successful completion of dose cohort 1, in the first-in-human Phase 1/2a clinical trial of AFM24, the EGFR/CD16A targeted innate cell engager for relapsed/ refractory patients with advanced EGFR-expressing solid tumors, the study was cleared to begin patient recruitment in dose cohort 2. The company reported that no dose limiting toxicity was observed in dose cohort 1.
Affimed researchers presented preclinical data on the pharmacology and safety of AFM24 at the AACR (Free AACR Whitepaper) Virtual Annual Meeting II.
Genentech Collaboration Update

In May 2020, Affimed confirmed that its novel BCMA targeted innate cell engager for the treatment of multiple myeloma has been partnered with Genentech, a member of the Roche Group.
Researchers from Genentech and Affimed co-authored a poster on the preclinical pharmacology and safety data of RO7297089 and presented data at the AACR (Free AACR Whitepaper) Virtual Annual Meeting II.
On clinicaltrials.gov, Genentech has posted a first-in-human Phase I, open-label, multicenter, global, dose-escalation study designed to evaluate the safety, tolerability, and pharmacokinetics of RO7297089.
Preclinical Pipeline Update

Affimed continues to progress AFM28 and AFM32 towards late stage preclinical development.
Management Appointments
Angus Smith was appointed to the position of Chief Financial Officer in June and will join the company in mid-July. Mr. Smith brings broad biopharmaceutical experience to the company including financial strategy and planning, capital markets, business development and operations.
The company announced the additions of Dr. Andreas Harstrick as Chief Medical Officer and Dr. Arndt Schottelius as Chief Scientific Officer earlier in the year. Dr. Harstrick, brings broad development expertise in solid tumor indications, including EGFR-expressing cancers. Dr. Schottelius brings extensive innate immunity expertise and a successful record of advancing discovery research into preclinical and clinical development.
First Quarter 2020 Financial Highlights
(Figures for the first quarter ended March 31, 2020 and 2019 are unaudited.)

As of March 31, 2020, cash, cash equivalents and current financial assets totaled €88.2 million compared to €104.1 million on December 31, 2019. In addition, the company raised €18.8 million (based on an exchange rate of $/€ of 1.1210 on June 19, 2020) net proceeds under its at-the-market ("ATM") program. The pro forma cash position of the company as of March 31, 2020, including the net proceeds from the ATM, would be €107.0 million. Based on its current operating plan and assumptions, Affimed anticipates that its cash, cash equivalents and current financial assets will support operations well into the first half of 2022.

Net cash used in operating activities for the quarter ended March 31, 2020, was €16.5 million, compared to €13.4 million for the quarter ended March 31, 2019. The increase is primarily due to higher expenditure related to research and development efforts.

Total revenue for the quarter ended March 31, 2020, was €5.1 million compared to €11.4 million for the same period of 2019. Revenue in both quarters is primarily attributable to the recognition of revenue from the Genentech collaboration in the respective years.

R&D expenses for the quarter ended March 31, 2020, were €11.4 million compared to research and development expenses of €8.0 million for the same period of 2019. The increase was primarily related to higher expenses for the AFM13 registration-directed study in pTCL, manufacturing activities for AFM13 clinical study material, and early stage development and discovery activities.

General and administrative (G&A) expenses for the quarter ended March 31, 2020, were €3.5 million compared to €2.4 million for the quarter ended March 31, 2019. The increase was primarily related to higher personnel expenses, a result of the strengthening of the talent pool, higher SOX compliance costs, legal, consulting and audit costs.

Net loss was €8.3 million, or €0.11 per common share, for the quarter ended March 31, 2020, compared to a net income of €1.9 million, or €0.03 per common share, for the quarter ended March 31, 2019.

Note on International Financial Reporting Standards (IFRS)
Affimed prepares and reports consolidated financial statements and financial information in accordance with IFRS as issued by the International Accounting Standards Board. None of the financial statements were prepared in accordance with Generally Accepted Accounting Principles in the United States. Affimed maintains its books and records in Euro.

Conference Call and Webcast Information
Affimed will host a conference call and webcast today, Tuesday, June 23, 2020 at 8:30 a.m. EDT to discuss first quarter 2020 financial results and recent corporate developments. The conference call will be available via phone and webcast. To access the call, please dial +1 (646) 741-3167 for U.S. callers, or +44 (0) 2071 928338 for international callers, and reference passcode 8594214 approximately 15 minutes prior to the call. A live audio webcast of the conference call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source A replay of the webcast will be accessible at the same link for 30 days following the call.

On June 23, 2020 BioInvent International AB ("BioInvent") (OMXS: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported the enrollment of the first patient in a Phase I/IIa clinical trial of BI-1206 in combination with anti-PD-1 therapy KEYTRUDA(pembrolizumab) for patients with solid tumors (Press release, BioInvent, JUN 23, 2020, View Source [SID1234561407]).

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The objective of this trial is to explore the safety and tolerability profile of the combination of BI-1206 with KEYTRUDA, to characterize the pharmacokinetic/pharmacodynamic (PK/PD) profile and to determine the recommended dose of BI-1206 when combined with KEYTRUDA. It will be conducted in several sites across the US and Europe and will assess potential signs of antitumoral activity, as well as exploring the expression of potential immunological markers that might be associated, and eventually predict clinical responses.

The Phase I/IIa trial is divided into part A, a dose escalation of BI-1206 in combination with the standard dose of KEYTRUDA, and part B, which will explore the activity of the combination treatment in patients with advanced lung cancer, melanoma and other types of malignancies. Patients will be refractory to or have progressed on previous treatments with anti-PD1/PDL1 targeting agents.

BI-1206 is a first-in-class monoclonal antibody that exquisitely targets FcgRIIb, the only inhibitory Fcg receptor, "the brakes" of the innate immune system. It is currently also being investigated in patients with non-Hodgkin lymphoma (NHL).

Martin Welschof, CEO of BioInvent, said, "We are very excited to be starting this trial in collaboration with MSD. Based on a strong scientific rationale the trial will explore a potentially important mechanism of resistance to anti-PD1/PDL1 targeting agents. We believe BI-1206’s potential ability to increase and enhance the response rates to anti-PD1 targeting agents such as KEYTRUDA may be a powerful approach for the future treatment of a broad range of solid and liquid tumors."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (NYSE: MRK), with whom BioInvent has a clinical trial collaboration and supply agreement for this study.