On August 12, 2020 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported its financial results for the quarter ended June 30, 2020 and provided a business update (Press release, Moleculin, AUG 12, 2020, View Source [SID1234563483]).

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Management Discussion

Walter Klemp, Chairman and CEO of Moleculin, stated, "Despite the difficult backdrop resulting from the global pandemic, we made tremendous progress across all three of our core technologies, particularly in our infectious disease platform of antimetabolites, bolstered our financial position, and added to our experienced leadership team. Importantly, we were pleased to progress our efforts to combat COVID-19, as WP1122, which is often referred to as a "prodrug" of 2-DG and one of our antimetabolites, demonstrated its potential in a number of pre-clinical studies and independent research publications. Independent research found 2-deoxy-D-glucose ("2-DG") reduced replication of SARS-CoV-2, the virus that causes COVID-19, by 100% in in vitro testing. A second independent publication at the University of Campinas in São Paulo further demonstrated the potential of WP1122’s mechanism of action as it showed SARS-CoV-2 infection is supported by elevated glucose levels and that inhibition of glycolysis with 2-DG effectively eliminated viral load in vitro. Additionally, two rounds of preclinical testing at one independent lab confirmed by a round of in-vitro testing at a second independent lab in a separate virus host cell line continued to demonstrate WP1122’s antiviral activity in SARS-CoV-2. We are very encouraged by this early demonstration of efficacy and are now even more motivated to continue to drive its development. Based on guidance from the FDA, we are pursuing additional studies in animal models, which we believe is the critical path to our expected timing, to further assess WP1122’s antiviral capability, with the goal of a possible IND filing in 2020, in preparation for beginning a human clinical trial thereafter."

Mr. Klemp continued, "Although we have expanded the scope and focus of our WP1122 program, our lead candidate, Annamycin, a ‘next generation anthracycline’ demonstrating little to no cardiotoxicity, still remains one of our key priories. The results from the Phase 1 portion of our US Phase 1/2 clinical trial in acute myeloid leukemia (AML) have been highly encouraging, as Annamycin met its primary endpoint and demonstrated a clean safety profile with no evidence of cardio-toxicity when delivered to patients at or below the lifetime maximum anthracycline dose established by the FDA. Following these strong results and an independent review of Annamycin, in which the independent expert concluded that he ‘does not see evidence of cardio-toxicity’, we received authorization from the Polish Department of Registration of Medicinal Products to increase the Phase 1 dose escalation portion of our clinical trial for the treatment of AML. We believe this to be a substantial development in the acceleration of our trial as it allows for the increase in dose escalation increments between cohorts from 30 mg/m2 to 60 mg/m2. This will enable our next cohort to increase to 300 mg/m2, assuming all requirements for safety are met with the 240 mg/m2 cohort, for which we are currently recruiting. With these dosing expectations, the Company believes that European dosing will increase in 2020, providing for a recommended Phase 2 Dose to be established in 2021. In addition to driving the development of Annamycin, during the second quarter we saw the advancement of WP1066, the lead molecule in Moleculin’s portfolio of immune stimulators and modulators of transcription. Importantly, Emory University began recruiting and treating patients in its Phase 1 clinical trial of WP1066 for the treatment of brain tumors in children. We are pleased by the progress of the trial, which has now enrolled and treated three patients. The Emory study, which is being at conducted at the Aflac Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta, represents a new approach for treating pediatric brain cancer and benefits from safety data generated in the ongoing clinical trial of WP1066 in adult brain tumors being conducted by MD Anderson Cancer Center."

Mr. Klemp concluded, "With our focus on the continued progression of our candidates and our expansion into infectious disease, we found it prudent to bolster our expertise. As a result, we made several strategic additions to our team at Moleculin. In March, we added Dr. Hongbo Zhai, who has two decades of research and development experience in pharmaceuticals and biotechnology, to our Science Advisory Board. To complement our expanded focus on COVID-19, we then added to our Science Advisory Board Dr. Dominique Schols, a leading virologist at the Rega Institute in Leuven, Belgium, and Dr. Richard Whitley, head of the NIAID Antiviral Drug Discovery and Development Center. With the additions to our team and the progress we made in all three of our programs, we believe we are well positioned to continue to build on the momentum we have achieved thus far in 2020."

Recent Milestones and Accomplishments:

Next Generation Anthracycline – Annamycin

Announced preclinical data corroborating the efficacy of Annamycin in lung metastases at AACR (Free AACR Whitepaper)
In process with the Polish regulatory authorities’ approval to open two additional clinical sites for the Phase 1/2 clinical study
Approved to accelerate European clinical trial in AML, URPL doubled dose escalation
Received additional positive safety data in EU AML trial, none of the 19 patients evaluated thus far have shown signs of cardiotoxicity
Received positive independent report confirming absence of cardiotoxicity (unlike currently approved anthracyclines)
Announced positive results and successful completion of the Phase 1 portion of the AML Phase 1/2 trial in the US
Found to be active against tumor metastases to the lung in pre-clinical testing
Confirmed anti-tumor efficacy of Annamycin in AML through new animal data
Expanded drug production to support positive clinical activity
Received FDA Fast Track designation
Immune/Transcription Modulators – WP1066 Portfolio

Reported findings that WP1066 used in combination with traditional whole brain radiation therapy (WBRT) resulted in long-term survivors and enhanced median survival time relative to monotherapy in mice with implanted human brain tumors
Emory University has treated three patients in a Phase 1 clinical trial of WP1066 for the treatment of brain tumors in children after receiving FDA Approval of IND and Emory University Clinical Trial Review Committee approval for STAT3 inhibitor in Investigator Initiated Clinical Trial
Patent protection filed by MD Anderson covering combination of immune stimulating/transcriptional modulator, including combination with radiation therapy
Presented preclinical pancreatic cancer data at American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting
Received Orphan Drug Designation from FDA
Infectious Disease and Metabolism/Glycosylation Inhibitors – WP1122 Portfolio

Independent research team at the University of Campinas in São Paulo, Brazil demonstrated that SARS-CoV-2 infection is supported by elevated glucose levels and that inhibition of glycolysis with 2-DG effectively eliminated viral load in vitro
Corroborated antiviral activity of WP1122 against coronavirus in pre-clinical testing at IIT Research Institute in another virus host cell line
Agreement with Sterling Pharma USA LLC for U.S. production of WP1122 to support expanded development efforts
Two rounds of preclinical assessment of the potential for WP1122 to address COVID-19 at ImQuest BioSciences demonstrated that WP1122 has an antiviral effect on HCoV-229E. The virus yield reduction assay demonstrated a 5 to 10-fold inhibition of coronavirus production by WP1122 when compared to untreated virus control.
University of Frankfurt found 2-DG to reduce replication of SARS-CoV-2, the virus that causes COVID-19, by 100% in in vitro testing
Patent filed by MD Anderson covering WP1122 as anti-viral drug candidate
Final data from Phase 1 proof-of-concept clinical trial for the treatment of cutaneous T-cell lymphoma
Began preclinical testing of new approach to Pancreatic cancer, opportunity to attack cancer by inhibiting tumor metabolism
Corporate Strategy

Appointed Dr. Whitley, who leads the Drug Discovery and Development Center for the National Institute of Allergy and Infectious Diseases, to Science Advisory Board
Added Dr. Dominique Schols, a leading virologist from the Rega Institute to the Moleculin development team as a consultant and a member of our Science Advisory Board
Appointed Dr. Hongbo Zhai, former Senior Faculty and Supervisor of Postdoctoral Fellow at University of California San Francisco, to Science Advisory Board
Anticipated 2020 Milestones

Achieving an MTD or a dose level at or above 300 mg/m2 in EU AML Phase 1/2 trial for Annamycin
Expanding our infectious disease portfolio via testing of WP1122 against CoV-2 in animal models and in vitro testing on CoV-2 and other hard to treat viruses with other antimetabolites – resulting in a cancer or virus related IND or its equivalent possibly being filed in 2020
IND submission for Annamycin for the treatment of tumor metastases to the lung
Moving WP1220 for the treatment of CTCL forward via a new Phase 2 clinical trial by filing an IND or its equivalent or attempt to join efforts with a strategic partner
Continued clinical testing in adult and pediatric brain tumors with WP1066 via physician sponsored trials
Financial Results for the Quarter Ended June 30, 2020

Research and development (R&D) expense was $3.3 million and $2.1 million for the three months ended June 30, 2020 and 2019, respectively. The increase of $1.2 million is mainly related to increased clinical trial activity, increased license fees and costs related to sponsored research agreements, costs related to manufacturing of additional drug product and two additional employees in R&D headcount.

General and administrative expense was $1.7 million and $1.5 million for the three months ended June 30, 2020 and 2019, respectively. The increase of $0.2 million was mainly attributable to increased stock-based compensation expense for annual employee stock options and increased costs for directors and officer’s liability insurance.

Loss from operations for the second quarter was $5.0 million compared to a net loss of $3.6 million for the second quarter of 2019. This increase was largely due to the above-mentioned increase in R&D.

Net loss for the second quarter of 2020 was $10.1 million, compared to a net loss of $1.2 million in the second quarter of 2019, and was attributed to the above-mentioned increase in R&D and the change in fair value on revaluation of warrant liability associated with warrants issued in conjunction with stock offerings. Changes in our stock price can result in a material gain or loss during the quarter related to the revaluation of our warrant liability. The loss from the change in the fair value of the warrant liability for the second quarter of 2020 was $5.1 million compared to a gain of $2.4 million in the same quarter in 2019. This is a non-cash item.

Liquidity and Capital Resources

As of June 30, 2020, we had cash and cash equivalents of $16.7 million and prepaid expenses and other of $3.0 million. We also had $1.9 million of accounts payable and $1.8 million of accrued expenses. A significant portion of the accounts payable and accrued expenses are due to work performed in relation to our clinical trials. For the six months ended June 30, 2020 and 2019, we used approximately $9.3 million and $9.2 million of cash in operating activities, respectively, which represents cash outlays for research and development and general and administrative expenses in such periods. For the six months ended June 30, 2020 and 2019, net proceeds from financing activities were $15.3 million and $20.8 million, respectively, predominately from the sale of our common stock and the exercise of warrants. Cash used in investing activities for the six months ended June 30, 2020 and 2019 was approximately $0.02 million and $0.03 million, respectively.

We believe that our existing cash and cash equivalents as of June 30, 2020 plus the $1.9 million cash raised subsequent to the quarter will be sufficient to fund our planned operations into the first quarter of 2021, without the issuance of additional equity for cash. Any such issuances should extend the funding of our planned operations beyond the first quarter of 2021. Such plans are subject to our stock price, market conditions, changes in planned expenses depending on clinical enrollment progress, the use of drug product or a combination thereof.

On August 12, 2020 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing reported pipeline updates, recent business highlights and second quarter 2020 financial results (Press release, Beam Therapeutics, AUG 12, 2020, View Source [SID1234563482]).

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"Throughout the first half of 2020, we made significant progress across all aspects of our business, culminating into naming the first two base editing development candidates from our portfolio. As we move closer to the clinic, we have also made the important strategic decision to establish a build-to-suit manufacturing facility, which will significantly enhance our capability to manufacture a wide range of base editing medicines," said John Evans, chief executive officer of Beam. "In addition, we continue to execute our strategy of establishing innovative partnerships to access new capabilities and to accelerate the development of base editors as a new class of precision genetic medicines for patients. Amidst the evolving COVID-19 situation, our team is performing well, and we remain on track to initiate IND-enabling studies in 2020 and file at least one Investigational New Drug application in 2021."

Giuseppe Ciaramella, Ph.D., president and chief scientific officer of Beam added, "Achieving our first development candidates with base editing is one of the most important milestones for our company yet. BEAM-101 and BEAM-102 are highly differentiated editing programs that may enable a one-time treatment option for patients with sickle cell disease. Both candidates are supported by promising preclinical data, and we are working to advance them to the next stage of development to assess the impact they could have in treating this devastating disease."

Base Editing Progress

First Base Editing Development Candidates Named for Treatment of Sickle Cell Disease: Beam is pursuing two differentiated base editing approaches to treat hemoglobinopathies and recently named the first two development candidates from its portfolio. Promising preclinical data from these two complementary editing programs were presented at the 23rd American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Virtual Annual Meeting.
BEAM-101 is an adenine base editor (ABE) that reproduces single base changes observed in individuals with hereditary persistence of fetal hemoglobin, or HPFH, in which elevated levels of fetal hemoglobin protect these individuals from the effects of sickle cell disease or beta-thalassemia.

BEAM-102 is an ABE that directly corrects the causative mutation in sickle cell disease, converting it into a naturally-occurring human hemoglobin variant, Hb-G Makassar. Individuals with the Makassar variant have normal hematologic parameters and no evidence of hemoglobin polymerization or sickling of red blood cells.

Preclinical Non-Human Primate Data Validating Beam’s ABE Technology Presented by Verve Therapeutics: Verve Therapeutics presented preclinical proof-of-concept data in non-human primates, utilizing ABE technology licensed from Beam, that demonstrate the successful use of base editing to turn off a gene in the liver and thereby lower blood levels of either LDL cholesterol or triglyceride-rich lipoproteins. Beam and Verve previously announced a strategic collaboration, under which Verve has exclusive access to Beam’s base editing, gene editing and delivery technologies for human therapeutic applications against certain cardiovascular targets. After the completion of Phase 1 studies, Beam has the ability to participate in future development and commercialization, and share 50 percent of U.S. profits and losses, for any product directed against these targets.
Recent Business Highlights

Lease Agreement for Beam’s In-House Manufacturing Facility to Support Future Product Development: On August 11, 2020, Beam entered into a lease agreement with Alexandria Real Estate Equities, Inc. to build a 100,000 square foot current Good Manufacturing Practice (cGMP) compliant manufacturing facility in Research Triangle Park, North Carolina that will support a broad range of clinical programs. Beam will invest up to $83 million over a five-year period and anticipates that the facility will be operational by the first quarter of 2023. The project will be facilitated, in part, by a Job Development Investment Grant (JDIG) approved by the North Carolina Economic Investment Committee, which authorizes potential reimbursements to Beam based on new tax revenues generated through the project. The facility will be designed to support manufacturing for the company’s ex vivo cell therapy programs in hematology and oncology and in vivo non-viral delivery programs for liver diseases, with flexibility to support manufacturing of its viral delivery programs, and ultimately, scale-up to support potential commercial supply.

Collaboration Established with Magenta Therapeutics to Evaluate MGTA-117 as a Conditioning Regimen for Base Editing Therapies: In June 2020, Beam and Magenta Therapeutics announced a non-exclusive research and clinical collaboration agreement to evaluate the potential utility of MGTA-117, Magenta’s targeted antibody-drug conjugate, for conditioning of patients with sickle cell disease and beta-thalassemia receiving Beam’s base editing therapies.

Strategic Alliance with Boston Children’s Hospital to Accelerate Translational and Clinical Research in Gene Editing for Complex Conditions: Beam has entered into a strategic alliance agreement with Boston Children’s Hospital designed to facilitate the development of disease-specific therapies using Beam’s base editing technology. Under the terms of the agreement, Beam will sponsor multiple research programs at Boston Children’s Hospital to advance translation of Beam’s pipeline across certain therapeutic areas of interest, including programs in sickle cell disease and pediatric leukemias and exploration of new disease areas. Boston Children’s Hospital will also serve as a clinical site in the future to advance bench-to-bedside translation of Beam’s pipeline.

Research Collaboration Established with Institute of Molecular and Clinical Ophthalmology Basel (IOB) to Develop Gene Editing Programs for Ocular Diseases: Beam has established a research collaboration agreement with the IOB, under which the partners will leverage IOB’s expertise in the field of ophthalmology and Beam’s base editing technology to advance programs directed to the treatment of certain ocular diseases, including Stargardt disease. Through this collaboration, IOB will leverage insights from ProgStar, an international collaboration studying the natural history study of Stargardt disease progression and helping to determine clinical outcome measures that could be used in clinical trials of future therapies. Additionally, IOB has developed technology that images the retina and choroid with better quality and dimension, as well as living models of the retina, which can be used to study the therapeutic impact base editing could have on ocular diseases.
Second Quarter 2020 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $228.0 million as of June 30, 2020.

Research & Development (R&D) Expenses: R&D expenses were $19.4 million for the quarter ended June 30, 2020, compared to $12.7 million for the quarter ended June 30, 2019. This increase was primarily due to the growth in the number of research and development employees and their related activities, as well as the expense allocated to R&D related to Beam’s leased facilities.

General &Administrative (G&A) Expenses: G&A expenses were $6.9 million for the quarter ended June 30, 2020, compared to $5.0 million for the quarter ended June 30, 2019. This increase was primarily a result of increased personnel related costs due to an increase in general and administrative employees and the cost of being a public company.

Net Loss: Net loss attributable to common stockholders was $34.2 million, or $0.69 per share, for the quarter ended June 30, 2020, compared to $21.1 million for the quarter ended June 30, 2019.

On August 12, 2020 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage immunotherapy company with a pipeline of novel T cell therapies for patients suffering from cancer, reported financial results for the second quarter ended June 30, 2020 and provided a corporate update (Press release, TCR2 Therapeutics, AUG 12, 2020, View Source [SID1234563481]).

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"The second quarter was incredibly strong for the Company as we continued to deliver significant progress in our clinical trials of TC-210 and TC-110 despite the pandemic. We are particularly pleased to update that, following the earlier announcement of five of our first five cancer patients showing tumor regression with TC-210, one patient is now a confirmed partial response based on independent central review and experienced further tumor regression from 42% to 75%," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "The initial data from TC-210 provide meaningful readthrough for our TRuC-T cell platform and we believe our robust preclinical pipeline supports our next phase of growth as we build a leading cell therapy company treating solid tumors. The strengthening of our balance sheet through our recent financing puts us in an excellent position to execute on our objectives and provide further clinical and scientific updates in 2020."

Recent Developments

TCR2 announced positive interim data from the first five patients treated in the Phase 1 portion of the TC-210 Phase 1/2 clinical trial for mesothelin-expressing solid tumors. All five patients showed tumor regression including two with RECIST partial response, one of which is now confirmed and two patients with stable disease through six months. Translational data further demonstrated TRuC-T cell expansion and activation. A manageable toxicity profile was observed with only one patient exhibiting TC-210-related non-hematologic grade >2 toxicity and no evidence of neurotoxicity or on-target, off-tumor toxicity.
TCR2 highlighted preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II of the Company’s proprietary T Cell Receptor Fusion Construct (TRuC) T cells that co-express a PD-1:CD28 switch receptor, which acts as a cell-intrinsic mechanism to overcome PD-L1/PD-L2 mediated immunosuppression. Upon repeated antigen stimulation, co-expression of the switch receptor in mesothelin-targeting TC-210 T cells enhanced TCR downstream signaling, prevented PD-L1-mediatied functional T-cell inhibition, significantly increased proliferation and augmented the production of growth and effector cytokines.
TCR2 announced the expansion of its leadership team with key business development and regulatory affairs cell therapy experts with the appointments of Gregg McConnell as Head of Business Development and Viera Muzithras as Vice President of Regulatory Affairs.
Anticipated Milestones

TCR2 anticipates an interim update from the Phase 1 portion of the TC-210 Phase 1/2 clinical trial for patients with mesothelin-expressing solid tumors in 2H20.
TCR2 anticipates an interim update from the Phase 1 portion of the TC-110 Phase 1/2 clinical trial for patients with CD19+ non-Hodgkin lymphoma or adult acute lymphoblastic leukemia in 2H20.
TCR2 anticipates certification of its manufacturing facility in Stevenage, UK, in 2H20.
TCR2 anticipates an IND filing for a third TRuC-T cell program in 2021.
Financial Highlights

Cash Position: TCR2 ended the second quarter of 2020 with $124.8 million in cash, cash equivalents, and investments compared to $158.1 million as of December 31, 2019. As a result of the recent equity offering, TCR2 raised an additional $134.6 million. Net cash used in operations was $16.0 million for the second quarter of 2020 compared to $10.2 million for second quarter of 2019. TCR2 continues to project net cash use of $60-70 million for 2020.

R&D Expenses: Research and development expenses were $12.9 million for the second quarter of 2020 compared to $8.8 million for the second quarter of 2019. The increase in R&D expenses is primarily related to increase in headcount, activities related to the Phase 1/2 clinical trial of TC-210 and activities related to the Phase 1/2 clinical trial of TC-110.

G&A Expenses: General and administrative expenses were $3.8 million for the second quarter of 2020 compared to $3.3 million for the second quarter of 2019. The increase in general and administrative expenses was primarily due to an increase in personnel costs and costs associated with operations as a public company.

Net Loss: Net loss was $16.2 million for the second quarter of 2020 compared to $11.1 million for the second quarter of 2019, driven predominantly by increased R&D expenses.
Upcoming Events

TCR2 Therapeutics management is scheduled to participate at the following upcoming conferences.

2020 Wedbush PacGrow Healthcare Virtual Conference: Ian Somaiya, Chief Financial Officer of TCR2 Therapeutics, will provide a company update using a virtual platform on Wednesday, August 12, 2020 at 10:55am ET
Cantor Fitzgerald Virtual Global Healthcare Conference: Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics, and Ian Somaiya, Chief Financial Officer of TCR2 Therapeutics, will provide a company update using a virtual platform on Wednesday, September 16, 2020 at 8:40am ET

On August 12, 2020 Vaccibody AS and Nektar Therapeutics (NASDAQ: NKTR) reported that the first patient has been dosed in the combination therapy of the Phase 1/2a study evaluating bempegaldesleukin (bempeg), Nektar’s CD122-preferential IL-2 pathway agonist, with VB10.NEO, Vaccibody’s personalized neoantigen cancer vaccine, in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) (Press release, Vaccibody, AUG 12, 2020, View Source [SID1234563480]).

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"We’re pleased to advance our collaboration with Vaccibody to evaluate the potential of bempeg given with a personalized vaccine, VB10.NEO, in patients with advanced head and neck cancer," said Jonathan Zalevsky, Ph.D., Chief Research & Development Officer at Nektar. "The rationale for this clinical study is supported by our promising preclinical data which demonstrated how a personalized cancer vaccine and a T cell proliferator can work synergistically to induce maximal expansion of vaccine-induced T cell clones, provide deep and durable responses and, at the same time, offer specific anti-tumor immunity."

VB10.NEO is designed to specifically activate a patient’s immune system to tumor-specific antigens, called neoantigens, while bempeg is designed to expand and proliferate tumor antigen-specific T cells in the periphery and in the tumor microenvironment. Addition of bempeg to VB10.NEO is intended to drive maximal expansion of vaccine-induced neoantigen-specific T cells for the treatment of cancer.

At the 2019 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, Vaccibody presented interim data for VB10.NEO in a group of patients with various solid tumor types who had all received multiple lines of prior anti-cancer therapy and had been treated with at least one checkpoint inhibitor (CPI) (nivolumab or pembrolizumab) for a range of 5 to 32 months. The data presented showed that 50 percent (7/14) of patients treated with VB10.NEO achieved clinical responses, including four patients with SCCHN. Clinical response was defined as either >10% reduction in the target lesions (as identified at screening) or converting progressive lesions into stable lesions (<20% increase, up to 37 weeks follow-up).

"We are pleased that our initial data with VB10.NEO demonstrated that the vaccine induced strong neoantigen-specific T cell responses and clinical benefit, particularly in patients who did not respond to checkpoint inhibitor monotherapy," said Agnete Fredriksen, President and Chief Scientific Officer of Vaccibody and continued: "We believe combining bempeg, a T cell stimulator, with VB10.NEO can further drive the expansion of VB10.NEO elicited neoantigen-specific T cells and potentially deepen and broaden anti-tumor activity. Siri Torhaug, Chief Medical Officer of Vaccibody added, "We are happy to announce the first patient dosed with the combined therapy of VB10.NEO and bempegaldesleukin and look forward to seeing the first read outs from this unique approach in patients with head and neck cancer."

Preclinical studies evaluating the combination of VB10.NEO and bempeg demonstrated the synergy of the two mechanisms to elicit greater breadth and depth of neoantigen-specific T cell responses as compared to each agent individually. In preclinical models of solid tumors, the combination induced strong immunogenic CD8+ T cell responses, and when combined with anti-PD-1, induced rapid, complete and durable tumor regression of small tumors, and long-lasting disease control of large tumors.1

About VB10.NEO
VB10.NEO, is Vaccibody’s proprietary therapeutic DNA vaccine which uses the patient’s own neoantigens for the personalized treatment of cancer patients. A phase 1/2a neoantigen clinical trial is currently enrolling patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell carcinoma of the head and neck. In clinical trials, VB10.NEO has demonstrated induction of strong neoantigen-specific immune responses which led to clinical responses in patients with locally advanced or metastatic disease.

About Bempegaldesleukin (NKTR-214)
Bempegaldesleukin is designed to stimulate cancer-killing immune cells in the body by targeting CD122 receptors found on the surface of these immune cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.2 In clinical and preclinical studies, treatment with bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro-environment.3,4

On August 12, 2020 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), an oncology-focused precision medicine company committed to the discovery and development of targeted therapeutics, reported financial results for the second quarter ended June 30, 2020 (Press release, Ideaya Biosciences, AUG 12, 2020, View Source [SID1234563479]).

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"This quarter was transformational for IDEAYA. We have cash runway into 2024, with quarter-end cash, cash equivalents and marketable securities of $172.0 million supplemented by $127.5 million aggregate gross proceeds received subsequently, including $100 million non-dilutive upfront cash and $20 million private placement equity investment from GSK. In addition, through our GSK strategic partnership and our Pfizer collaboration and supply agreement, we have established an attractive cost structure and retained significant future upside across our pipeline, while also creating opportunities for non-dilutive cash milestones of approximately $3 billion across three programs with GSK. We also nominated MAT2A development candidate IDE397, initiated the IDE196 and binimetinib Phase 1 combination, and met the criteria for IDE196 Phase 2 expansion in skin melanoma. As we celebrate our five-year anniversary, we have built a strong foundation to create the industry leading Synthetic Lethality-focused precision medicine oncology company," said Yujiro S. Hata, Chief Executive Officer and President of IDEAYA Biosciences.

GlaxoSmithKline Strategic Partnership

IDEAYA and GSK entered into a strategic partnership in Synthetic Lethality focused on IDEAYA’s MAT2A, Pol Theta, and Werner Helicase programs – each of which has a strong rationale for collaborating, including potential clinical combinations with GSK precision medicine therapeutics. The strategic partnership includes small molecule and protein degrader modalities.

IDEAYA retains all rights and interests in its other pipeline assets, including preclinical programs targeting PARG and a proprietary DNA Damage Target, as well as its clinical candidate IDE196 for patients having tumors harboring GNAQ or GNA11 hotspot mutations.

Program Updates

Key highlights for IDEAYA’s pipeline programs include:

MAT2A

IDEAYA’s lead synthetic lethality research program targets MAT2A for solid tumors with MTAP deletions, a patient population estimated to represent approximately 15% of solid tumors. IDEAYA continues to lead research and development on the MAT2A program through early clinical development. Subject to exercise of its option, GSK will lead later stage global clinical development. Highlights:

Designated MAT2A inhibitor IDE397 as a development candidate;
Demonstrated IDE397 in vivo dose-dependent efficacy and tumor regression (with >100% TGI, or tumor growth inhibition) as monotherapy in an endogenous non-small cell lung cancer MTAP-null PDX model;
Initiated good laboratory practice (GLP)-compliant toxicology studies with IDE397 in two species;
On track for IND submission to the FDA for IDE397 in the fourth quarter of 2020, subject to satisfactory completion of GLP toxicology studies;
Plan to initiate a Phase 1 clinical trial for clinical evaluation of IDE397 as monotherapy in the first half of 2021, subject to effectiveness of the IND; and
IDEAYA and GSK are evaluating a potential phase 1 combination clinical trial for IDEAYA’s MAT2A inhibitor (IDE397) and GSK’s Type I PRMT inhibitor (GSK3368715).
PARG

IDEAYA is advancing preclinical research for an inhibitor of poly (ADP-ribose) glycohydrolase, or PARG. PARG inhibitors have shown synthetic lethality with tumors harboring BRCA2 mutations, impaired base excision repair, or BER, and potentially other genetic and/or molecular signatures. Highlights:

Demonstrated in vivo proof of concept in a relevant animal model having a replication stress genetic signature;
Validating a potential synthetic lethality biomarker for identifying tumor cells having sensitivity to a PARG inhibitor;
Observed monotherapy PARG inhibitor in vivo efficacy in multiple PDX models, including tumor regression; and
Targeting to identify a PARG inhibitor development candidate in 2021
Pol Theta

IDEAYA’s Pol Theta program targets tumors with BRCA or other homologous recombination deficiency (HRD) mutations. IDEAYA and GSK will collaborate on ongoing preclinical research, including small molecules and protein degraders, and GSK will lead clinical development for the Pol Theta program. Subject to such preclinical studies, we are targeting to file an IND for a Pol Theta inhibitor in 2021. Highlights:

Demonstrated in vivo efficacy with tumor regression in BRCA2 -/- xenograft model with IDEAYA Pol Theta inhibitor in combination with niraparib, a GSK PARP inhibitor
Werner Helicase

IDEAYA is advancing preclinical research for an inhibitor targeting Werner Helicase for tumors with high microsatellite instability (MSI). IDEAYA and GSK will collaborate on ongoing preclinical research, and GSK will lead clinical development for the Werner Helicase program.

Expanding Synthetic Lethality Pipeline and Synthetic Lethality Platform

IDEAYA has initiated additional preclinical synthetic lethality research programs, including for a DNA Damage Target (DDT), for patients with solid tumors characterized by a proprietary biomarker or gene signature.

IDEAYA continues to build its Synthetic Lethality platform, investing in target identification, biomarker discovery and drug discovery, including small molecules and protein degraders, to create the industry leading Synthetic Lethality and DNA Damage based pipeline.

IDE196

IDEAYA continued to execute on its clinical trial, initiated in June 2019, to evaluate IDE196 in Metastatic Uveal Melanoma (MUM) and Non-MUM solid tumors harboring activating GNAQ/11 mutations. The clinical development strategy for IDE196 is focused on evaluating IDE196 combination therapy for the MUM indication, and evaluating IDE196 monotherapy in non-MUM GNAQ/11 hotspot mutation solid tumors, such as skin melanoma.

Combination Therapy

IDEAYA is enrolling MUM patients into a combination arm of the IDE196 Phase 1/2 clinical trial to evaluate safety and efficacy of IDE196 in combination with binimetinib, a MEK inhibitor. We may also evaluate IDE196 / binimetinib combination therapy in patients having other solid tumors with activating GNAQ/11 hotspot mutations, such as skin melanoma. The combination arm is being conducted under a clinical trial collaboration and supply agreement with Pfizer Inc., pursuant to which Pfizer supplies us with their MEK inhibitor, binimetinib; the companies established a Joint Development Committee with Pfizer to facilitate combination arm drug supply, trial initiation and ongoing development. Highlights:

First-Patient-In (FPI) of a MUM patient for IDE196 / binimetinib combination arm of the IDE196 clinical trial in June 2020;
Initiated dosing into a first cohort of the IDE196 / binimetinib dose escalation portion of combination arm; and
Interim data from evaluation of IDE196 / binimetinib combination therapy anticipated in late 2021 to early 2022.
Monotherapy

IDEAYA is actively enrolling into the IDE196 monotherapy Phase 2 tissue-type agnostic basket arm in Non-MUM solid tumors having GNAQ or GNA11 hotspot mutations, including skin melanoma. Highlights:

Clinical protocol criteria met for cohort expansion in cutaneous melanoma, or skin melanoma. Of 4 evaluable skin melanoma patients harboring GNAQ/11 hotspot mutations (out of 5 total enrolled; excluding 1 non-evaluable), a 100% Disease Control Rate was observed, and one confirmed partial response (cPR) was determined by RECIST 1.1 guidelines;
The skin melanoma patient with cPR observed an initial partial response (-31.1%) at 8 weeks, which was sustained at 20 weeks (-37%) with reduction in target liver lesion and inguinal lymph node. Treatment with IDE196 is ongoing as of August 1, 2020;
Dosed first leiomyosarcoma patient in the Phase 2 GNAQ/11 basket arm, expanding the tissue-agnostic approach to additional solid tumors;
Established a relationship with CARIS through which we are accessing their network of clinical trial sites into which we can enroll qualifying patients having tumors harboring GNAQ/11 hotspot mutations; and
Interim data from the monotherapy arm of the Phase 2 basket trial anticipated in first half of 2021.
General

IDEAYA completed IDE196 tablet formulation and successfully introduced the tablet in the ongoing clinical trial, including the IDE196 / binimetinib combination arm and the GNAQ/11 basket arm.

IDEAYA completed 13-week GLP-compliant toxicology studies in two species, with receipt of submission-ready audited draft reports.

IDEAYA continues to monitor Covid-19 and its potential impact on clinical trials and timing of clinical data results. Covid-19 infection rates have increased recently in several states in which our clinical trial sites are located. As such, ongoing monitoring of enrolled patients, including obtaining patient computed tomography (CT) scans, may be impacted, and new patient enrollment into the Phase 2 expansion arm for IDE196 as a monotherapy in non-MUM solid tumors having GNAQ or GNA11 hotspot mutations may be delayed; the specific impacts are currently uncertain.

Corporate Updates

IDEAYA anticipates that existing cash, cash equivalents, and short-term and long-term marketable securities of $172.0 million as of June 30, 2020, together with the additional aggregate gross proceeds of $127.5 million received from GSK as up-front cash payment and from equity investments subsequent to June 30, 2020, will be sufficient to fund planned operations into 2024, and through potential achievement of multiple preclinical and clinical milestones across multiple programs.

Our updated corporate presentation is available on our website, in the Presentations section of our Investor Relations page. See: View Source .

Financial Results

As of June 30, 2020, IDEAYA had cash, cash equivalents, and short-term and long-term marketable securities totaling $172.0 million. This compared to cash, cash equivalents and short-term marketable securities of $100.5 million at December 31, 2019. The increase was primarily due to $93.6 million in net proceeds from IDEAYA’s follow-on public offering through June 30, 2020.

Research and development (R&D) expenses for the three months ended June 30, 2020 totaled $8.6 million compared to $8.9 million for the same period in 2019. The decrease was primarily due to a decrease in R&D headcount and laboratory supply costs, offset by an increase in costs related to our IDE196 clinical trial and the advancement of IDE397 through preclinical studies.

General and administrative (G&A) expenses for the three months ended June 30, 2020 totaled $4.0 million compared to $2.4 million for the same period in 2019. The increase was primarily due to an increase in G&A headcount costs, director and officer insurance policy premiums, costs related to our shelf registration statement filing on Form S-3, and an increase in legal expenses.

The net loss for the three months ended June 30, 2020 was $12.4 million compared to $10.7 million for the same period in 2019. Total stock compensation expense for the three months ended June 30, 2020 was $0.8 million compared to $0.5 million for the same period in 2019.