On August 13, 2021 F-star reported that entered into a Sales Agreement (the "2021 Sales Agreement") with SVB Leerink LLC ("SVB Leerink") with respect to an at-the-market offering program under which the Company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.0001 per share (the "Common Stock"), having an aggregate offering price of up to $50.0 million (the "Placement Shares") through SVB Leerink as its sales agent (Filing, 8-K, F-star, AUG 13, 2021, View Source [SID1234586692]). The issuance and sale, if any, of the Placement Shares by the Company under the 2021 Sales Agreement is subject to the effectiveness of the Company’s registration statement on Form S-3 (File No. 333-258783), which was filed with the Securities and Exchange Commission on August 13, 2021.

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Upon delivery of a placement notice and subject to the terms and conditions of the 2021 Sales Agreement, SVB Leerink may sell the Placement Shares by any method permitted by law deemed to be an "at the market" offering as defined in Rule 415 of the Securities Act of 1933, as amended, including, without limitation, sales made through The Nasdaq Capital Market or on any other existing trading market for the Common Stock. SVB Leerink will use commercially reasonable efforts to sell the Placement Shares from time to time, based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions the Company may impose). The Company will pay SVB Leerink a commission equal to three percent (3%) of the gross sales proceeds of any Placement Shares sold through SVB Leerink under the 2021 Sales Agreement, and also has provided SVB Leerink with customary indemnification and contribution rights.

The Company is not obligated to make any sales of Common Stock under the 2021 Sales Agreement. The offering of Placement Shares pursuant to the 2021 Sales Agreement will terminate upon the earlier of (i) the sale of all Placement Shares subject to the 2021 Sales Agreement or (ii) termination of the 2021 Sales Agreement in accordance with its terms.

Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C., counsel to the Company, has issued a legal opinion relating to the Placement Shares. A copy of such legal opinion, including the consent included therein, is attached as Exhibit 5.1 hereto.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On August 13, 2021 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved WELIREG, an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery (Press release, Merck & Co, AUG 13, 2021, View Source [SID1234586584]). The recommended dose of WELIREG (40 mg tablets) is 120 mg once daily until disease progression or unacceptance toxicity. The approval is based on results from the open-label Study 004 trial (N=61), where the major efficacy endpoint was overall response rate (ORR) in patients with VHL-associated RCC.

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WELIREG is the first HIF-2α inhibitor therapy approved in the U.S. As an inhibitor of HIF-2α, WELIREG reduces transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis and tumor growth.

The WELIREG label contains a boxed warning that exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective. WELIREG can cause severe anemia that can require a blood transfusion. Monitor for anemia before initiation of WELIREG and periodically throughout treatment. WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Monitor oxygen saturation before initiation of and periodically throughout treatment with WELIREG. For more information, see "Selected Safety Information" below.

"VHL disease is a rare and serious condition. Until today, there were no systemic therapies approved to help treat patients diagnosed with certain types of VHL-associated tumors," said Dr. Eric Jonasch, principal investigator of Study 004 and professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. "The approval of WELIREG, which is based on data showing an overall response rate across three different types of VHL-associated tumors, addresses this significant unmet need by introducing a new option for physicians and their patients impacted by this disease."

"WELIREG is the first and only approved systemic therapy for patients with certain types of VHL-associated tumors, representing an important new treatment option for patients affected by this rare condition," said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. "Today’s approval of WELIREG is a significant milestone and is a testament to Merck’s commitment to bring forward innovative new treatment options for more patients."

"The approval of a non-surgical treatment option is meaningful for helping patients with certain types of VHL-associated tumors," said Dr. Ramaprasad Srinivasan, head, Molecular Cancer Therapeutics Section, Urologic Oncology Branch, National Cancer Institute (NCI), and principal investigator on the Cooperative Research and Development Agreement (CRADA) under which the NCI served as a site in Study 004. "In Study 004, nearly half of all patients with VHL-associated renal cell carcinoma, as well as the majority of patients with VHL-associated central nervous system hemangioblastomas or pancreatic neuroendocrine tumors, who were treated with WELIREG experienced a reduction of their respective tumor size. The FDA’s approval of WELIREG marks an important step forward by introducing a systemic therapy that has the potential to improve the current treatment paradigm for patients with certain types of VHL-associated tumors."

Merck is working to optimize production of WELIREG to allow for a sustainable supply to meet anticipated U.S. demand. Commercial supply is expected to be available by early September.

Data Supporting the Approval

The approval was based on data from Study 004 (ClinicalTrials.gov, NCT03401788), an open-label trial in 61 patients with VHL-associated RCC diagnosed based on a VHL germline alteration and with at least one measurable solid tumor (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNET. CNS hemangioblastomas and pNET in these patients were diagnosed based on the presence of at least one measurable solid tumor in the brain/spine or pancreas, respectively, as defined by RECIST v1.1 and identified by an independent review committee (IRC). The study excluded patients with metastatic disease. Patients received WELIREG at a dose of 120 mg once daily until progression of disease or unacceptable toxicity. In Study 004, the median duration of exposure to WELIREG was 68 weeks (range, 8.4 to 104.7).

The study population characteristics were: median age of 41 years (range, 19 to 66), 3.3% age 65 or older; 53% male; 90% white, 3.3% Black or African American, 1.6% Asian, and 1.6% Native Hawaiian or other Pacific Islander; 82% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 16% had an ECOG PS of 1, and 1.6% had an ECOG PS of 2; and 84% had VHL type I disease. The median diameter of RCC target lesions per central IRC was 2.2 centimeters (range, 1 to 6.1). Median time from initial radiographic diagnosis of VHL-associated RCC tumors that led to enrollment on Study 004 to the time of treatment with WELIREG was 17.9 months (range, 2.8 to 96.7). Seventy-seven percent of patients had prior surgical procedures for RCC.

The major efficacy endpoint for the treatment of VHL-associated RCC was ORR measured by radiology assessment using RECIST v1.1 as assessed by IRC. Additional efficacy endpoints included duration of response (DoR) and time to response (TTR).

In patients with VHL-associated RCC (n=61), WELIREG showed an ORR of 49% (95% CI, 36-62); all responses were partial responses. Median DoR had not yet been reached (range, 2.8+ to 22.3+ months); among responders, 56% (n=17/30) were still responding after at least 12 months. Median TTR was eight months (range, 2.7 to 19).

In patients with VHL-associated CNS hemangioblastomas (n=24), WELIREG showed an ORR of 63% (95% CI, 41-81), with a complete response rate of 4% (n=1) and a partial response rate of 58% (n=14). Median DoR had not yet been reached (range, 3.7+ to 22.3+ months); among responders, 73% (n=11/15) were still responding after at least 12 months. Median TTR was three months (range, 3 to 11).

In patients with VHL-associated pNET (n=12), WELIREG showed an ORR of 83% (95% CI, 52-98), with a complete response rate of 17% (n=2) and a partial response rate of 67% (n=8). Median DoR had not yet been reached (range, 10.8+ to 19.4+ months); among responders, 50% (n=5/10) were still responding after at least 12 months. Median TTR was eight months (range, 3 to 11).

Serious adverse reactions occurred in 15% of patients who received WELIREG, including anemia, hypoxia, anaphylaxis reaction, retinal detachment and central retinal vein occlusion (1 patient each). Permanent discontinuation of WELIREG due to adverse reactions occurred in 3.3% of patients. Adverse reactions that resulted in permanent discontinuation of WELIREG were dizziness and opioid overdose (1.6% each).

Dosage interruptions of WELIREG due to an adverse reaction occurred in 39% of patients. Adverse reactions that required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache and influenza-like illness. Dose reductions of WELIREG due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction that required dose reduction was fatigue (7%).

The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients treated with WELIREG were decreased hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%) and nausea (31%).

About Von Hippel-Lindau Disease

The incidence of von Hippel-Lindau (VHL) syndrome is estimated to be one in 36,000 individuals. This is a rare genetic disease with an estimated incidence of 10,000 people in the U.S. Patients with VHL disease are at risk for benign blood vessel tumors as well as some cancerous ones, including renal cell carcinoma.

WELIREG (belzutifan) Indication in the U.S.

WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

Selected Safety Information

Warning: Embryo-Fetal Toxicity

Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective.

Anemia

WELIREG can cause severe anemia that can require blood transfusion. In Study 004, anemia occurred in 90% of patients and 7% had Grade 3 anemia. In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, anemia occurred in 76% of patients and 28% had Grade 3 anemia.

Monitor for anemia before initiation of and periodically throughout treatment. Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers due to potential increases in exposure that may increase the incidence or severity of anemia.

Transfuse patients as clinically indicated. For patients with hemoglobin <9g/dL, withhold WELIREG until Hb≥9g/dL, then resume at reduced dose or permanently discontinue depending on the severity of anemia. For life threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥9g/dL, then resume at a reduced dose or permanently discontinue.

The use of erythropoiesis stimulating agents (ESAs) for treatment of anemia is not recommended in patients treated with WELIREG.

Hypoxia

WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. In Study 004, hypoxia occurred in 1.6% of patients. In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, hypoxia occurred in 29% of patients; 16% were Grade 3 hypoxia.

Monitor oxygen saturation before initiation of and periodically throughout treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.

Embryo-Fetal Toxicity

Based on findings in animal studies, WELIREG may cause fetal harm when administered to a pregnant woman.

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Adverse Reactions

In Study 004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).

The most common adverse reactions (≥25%) were decreased hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, the following additional adverse reactions have been reported: edema, cough, musculoskeletal pain, vomiting, diarrhea, and dehydration.

Drug Interactions

Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

Coadministration of WELIREG with CYP3A4 substrates, including hormonal contraceptives, decreases concentration of CYP3A4 substrates, which may reduce the efficacy of these substrates. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

Females and Males of Reproductive Potential

WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Based on findings in animals, WELIREG may impair fertility in males of reproductive potential and the reversibility of this effect is unknown.

Pediatric Use

Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On August 13, 2021 A3P Biomedical AB reported that the publication of the STHLM3 MRI trial including 12,750 men has been fast tracked and is now published in the renowned peer-reviewed scientific publication The Lancet Oncology1 (Press release, A3P Biomedical, AUG 13, 2021, View Source [SID1234586570]).

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Results from the STHLM3 MRI trial, published in The Lancet Oncology, demonstrated that the combination of A3P Biomedical’s proprietary blood test Stockholm3 with Magnetic resonance imaging (MRI) in a population based prostate cancer screening program decreases unnecessary biopsies by 74% compared to standard of care, while maintaining detection of significant cancer.

Furthermore, Stockholm3 reduces MRI procedures with 36% compared to PSA. These significant improvements may enable population-based prostate cancer screening.

"To get fast track publication in The Lancet Oncology in addition to winning first prize for best abstract at the recent EAU2 congress shows the significance of the data. A considerable reduction in unnecessary biopsies as well as MRI procedures, which creates bottlenecks, is a major improvement and provides the basis for accelerating the implementation of general prostate cancer screening. The evidence for the Stockholm3 test is based on clinical trials on more than 80,000 men", said David Rosén, CEO at A3P Biomedical.

The STHLM3 MRI-trial is a randomized screening-by-invitation trial, comparing the standard test PSA with the Stockholm3 blood test when used with MRI-targeted or systematic biopsies for prostate cancer detection. 12,750 men in the age of 50-74 years participated in the trial. Compared to standard screening by PSA and systematic biopsies, Stockholm3 combined with MRI-targeted biopsies was associated with 74% fewer unnecessary biopsy procedures and 69% fewer overdiagnosed low-grade cancers, while maintaining detection of significant cancer.

The AUC (area under the receiver-operating characteristic curve) for significant cancer in the standard biopsy arm was 0.76 (95%CI 0.72-0.80) and 0.60 (95%CI 0.54-0.65) for Stockholm3 and PSA, respectively, equalling a 27% improvement in AUC. Furthermore, by using Stockholm3 instead of PSA prior to MRI, the number of MRI procedures were reduced by 36% and the unnecessary biopsies were reduced an additional 18%.

Current standard of care starts with PSA testing. However, the poor specificity of PSA leads to unnecessary biopsies and overdiagnosis of low-grade prostate cancers, which has been a major barrier to the use of PSA in population-based screening.

"The healthcare providers in the Nordics that already transitioned to Stockholm3 have demonstrated that in clinical practice even better results are achieved than in clinical screening trials; 100% more aggressive cancers found, 50% reduction of unnecessary biopsies and 17 to 25% lower costs. A3P Biomedical is committed to making the Stockholm3 test available worldwide and look forward to work with current and new partners to improve men’s health and quality of life", David Rosén further commented.

About Stockholm3
Stockholm3 is a blood test that combines protein markers, genetic markers, clinical data, and a proprietary algorithm, to predict the risk of aggressive prostate cancer. In clinical practice, Stockholm3 finds 100%more aggressive prostate cancers and reduces 50%of unnecessary biopsies compared to current practice with PSA (1).

Stockholm3 has been evaluated in clinical studies with more than 80,000 men. Data from the latest pivotal study, a randomized study including 12,750 men, was published in The Lancet Oncology in 2021. Multiple studies have been published in high-impact journals, including a previous study with 58,000 men, published in The Lancet Oncology in 2015 (1).

Based on robust peer-reviewed clinical data, leading Nordic healthcare providers such as Capio S:t Görans Hospital in Sweden and Stavanger University Hospital in Norway have replaced PSA with Stockholm3. Patients benefit from a more precise test (increasing sensitivity and specificity) and healthcare providers also benefit from direct cost savings of 17 to 25%(1).

(1) Publications, results and clinical validation.

About prostate cancer
Prostate cancer is the second most common male cancer, and the fifth leading cause of cancer related death in men worldwide. In 2020, 1.4 million men were diagnosed with prostate cancer and 375,000 deaths were reported by GLOBOCAN. Incidence of prostate cancer is expected to increase by 70% until 2040, driven by an aging population.

On August 13, 2021 BioAtla, Inc. (Nasdaq: BCAB), a global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) antibody therapeutics, reported financial results for the second quarter of 2021 and provided an update on its business (Press release, BioAtla, AUG 13, 2021, View Source [SID1234586569]).

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"BioAtla is advancing potentially registration-enabling Phase 2 clinical trials for our two lead CAB product candidates. With strong financial resources, we are also broadening our development pipeline to include several additional ADC and bispecific CAB candidates," stated Jay M. Short, Ph.D., Chairman, Chief Executive Officer and co-founder of BioAtla, Inc. "Our clinical objectives in 2021 include providing Phase 2 interim data readouts by year-end for CAB-AXL-ADC and CAB-ROR2-ADC. Our Phase 1 trials for these product candidates demonstrated encouraging results in difficult to treat cancer indications, particularly in patients with late-stage disease refractory to other lines of therapy," added Scott Smith, President of BioAtla.

Advancing clinical trials for lead candidates

BA3011 (Mecbotamab Vedotin)
We are developing BA3011, CAB-AXL-ADC, a conditionally activated antibody drug conjugate targeting the receptor tyrosine kinase AXL, as a potential therapeutic for multiple solid tumor types, including soft tissue and bone sarcoma, non-small cell lung cancer (NSCLC) and ovarian cancer, with other potential indications in the future. On March 1, 2021 the Office of Orphan Drug Products (OODP) at FDA granted Orphan Drug Designation to BA3011 for the treatment of soft tissue sarcoma. Phase 1 results in sarcoma patients have been submitted for presentation at the Connective Tissue Oncology Society (CTOS) 2021 Annual Meeting in November. As previously indicated, we have initiated a potentially registration-enabling Phase 2 clinical trial (BA3011-001) of BA3011 given as monotherapy or in combination with a PD-1 inhibitor in soft tissue and primary bone sarcoma patients 12 years and older that are high AXL tumor membrane expressors (AXL high), and a Phase 2 study (BA3011-002) in AXL high NSCLC patients that have previously progressed on PD-1/L1, EGFR or ALK inhibitor therapy. Enrollment continues in our sarcoma Phase 2 trial in the U.S. and initiated in Asia this quarter with first patient dosing in Taiwan. A pre-planned Independent Data Monitoring Committee (IDMC) was held and the IDMC recommended BioAtla continue the BA3011-001 study without modifications. Additional Interim analyses in the sarcoma and NSCLC trials are anticipated this year and early 2022. In addition, the commencement of a multi-center investigator-initiated Phase 2 clinical trial for BA3011 in platinum-resistant ovarian cancer in combination with a PD-1 inhibitor has been approved by Health Canada and is expected to begin enrollment in the second half of this year in Canada and the United States.

BA3021 (Ozuriftamab Vedotin)
BA3021, CAB-ROR2-ADC, is a CAB antibody drug conjugate directed against ROR2, a receptor tyrosine kinase that is overexpressed across many different solid tumors including lung, head and neck, melanoma and breast. We are developing BA3021 as a potential therapeutic for multiple solid tumor types, including NSCLC, melanoma, squamous cell cancer of the head and neck (SSCHN) and ovarian cancer. Based on phase 1 data we believe BA3021 has broad potential as a cancer therapy for patients with advanced solid tumors that have previously progressed on a PD-1 inhibitor. We are enrolling a Phase 2 trial of BA3021 monotherapy or in combination with a PD-1 inhibitor in ROR2 high melanoma patients that have previously progressed on PD-1/L1 inhibitor and ROR2 high NSCLC patients that have previously on PD-1/L1, EGFR or ALK inhibitor therapy. A Phase 2 study in ROR2 high SSCHN patients is anticipated to initiate in second half of 2021. A BA3021 in combination with a PD-1 inhibitor Phase 2 clinical trial for platinum-resistant ovarian cancer has been approved by Health Canada and is expected to begin enrollment in the second half of this year in Canada and the United States.

BA3071
BA3071, is a CAB anti-CTLA-4 antibody that is being developed as an immuno-oncology agent with the goal of delivering efficacy comparable to the approved anti-CTLA-4 antibody, ipilimumab, but with lower toxicities due to the CAB’s tumor microenvironment-restricted activation. Like BA3011, BA3021 and our other CAB candidates, BA3071 is designed to be conditionally and reversibly activated in the tumor microenvironment via the Protein-associated Chemical SwitchTM or PaCSTM mechanism discovered by BioAtla scientists. This proprietary system enables reduction of systemic toxicity and potentially enables safer combination therapies, such as with anti-PD-1 antibody checkpoint inhibitors in the case of BA3071. We are currently in a global collaboration with BeiGene, and are developing BA3071 as a potential therapeutic for multiple solid tumor indications, including renal cell carcinoma, NSCLC, small cell lung cancer, hepatocellular carcinoma, melanoma, bladder cancer, gastric cancer and cervical cancer. Our goal is to initiate a Phase 1/2 study for BA3071 in 2021.

Plans to advance development of several bispecific CAB candidates
We have also leveraged our CAB technology to develop bispecific antibodies, which bind both a tumor-specific antigen and a T cell receptor (CD3) using CAB antigen-binding domains. With this design, bispecific antibodies can induce potent T cell responses against tumors expressing the tumor target antigen. We have shown in preclinical experiments that our CAB bispecific molecules meet or exceed the activity of conventional bispecifics and reduce systemic activation of potentially fatal immune responses. We advanced two CAB bispecific antibody product candidates, EpCAM/CD3 and B7-H3/CD3, into IND-enabling studies in the second half of 2020. We also are evaluating additional candidates including EGFR and Nectin-4 for CAB CD3 bispecific modalities. Nectin-4 is also progressing as a CAB ADC candidate. Overall, we are advancing multiple pre-clinical assets with the potential to submit up to four US INDs by the end of 2022 for our CAB bispecific or ADC molecules.

Second quarter 2021 financial results
Cash and cash equivalents as of June 30, 2021 were $207.6 million. We expect current cash and cash equivalents will be sufficient to fund planned operations into 2023.

Research and development (R&D) expenses were $14.9 million for the quarter ended June 30, 2021 compared to $2.9 million for the same quarter in 2020. We expect our R&D expenses to increase substantially for the foreseeable future as we continue to invest in R&D activities to advance our product candidates, and our clinical programs and expand our product candidate pipeline.

General and administrative (G&A) expenses were $15.9 million for the quarter ended June 30, 2021 compared to $1.8 million for the same quarter in 2020. We expect our G&A expenses to increase as a result of operating as a public company. In addition, we expect our intellectual property expenses to increase as we expand our intellectual property portfolio.

Net loss for the second quarter ended June 30, 2021 was $30.4 million compared to a net loss of $6.2 million for the same quarter in 2020. Net cash used in operating activities for the first six months of 2021 was $28.5 million compared to net cash used in operating activities of $6.9 million for the same period in 2020.

On August 13, 2021 GT Biopharma, Inc. ("GT Biopharma" or the "Company") (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary natural killer (NK) cell engager (TriKE) protein biologic technology platform, reported a general business update of events in the second quarter ending June 30, 2021 (Press release, GT Biopharma, AUG 13, 2021, View Source [SID1234586568]).

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"I am pleased with the corporate and clinical development milestones that GT Biopharma continues to achieve throughout the first half of 2021," said Anthony J. Cataldo, GT Biopharma’s Chairman and Chief Executive Officer. "The Company continues to demonstrate that our proprietary TriKE platform technology is both safe and efficacious, demonstrated through our recent positive, interim data announcement of our ongoing Phase I/II dose expansion clinical trial of GTB-3550 TriKE. The TriKE platform is robust, focusing not only on hematologic cancers but also on solid tumor cancers such as lung, prostate, breast and ovarian cancers. The TriKE platform includes our B7H3, PD-L1 and HER2 TriKE product candidates. Our breadth of indications and the utility of TriKE as a therapeutic agent reduces the risk profile of our therapeutic platform and pipeline. Our collaborative efforts were strengthened through the Company’s research agreement with Dr. Jeffrey S. Miller and the University of Minnesota, and signifies that we are continuing to hit important strides in the clinic. These positive milestones reinforce GT Biopharma’s need to continue developing this first-in-human treatment for patients living with AML, MDS and other CD33+ hematologic cancers."

Clinical Highlights

Reported Positive, Interim Data Results from First-in-Human GTB-3550 TriKE Phase I Clinical Trial for the Treatment of Refractory/Relapsed Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): In June 2021, GT Biopharma and Dr. Jeffrey S. Miller presented positive, interim results from the Phase I dose-escalation portion of the Phase I/II dose expansion clinical trial of GTB-3550 TriKE at the 2021 Raymond James Human Health Innovation Conference. Results demonstrated that 57% of patients achieved significant reduction in AML/MDS cancer cell burden, with one patient reaching up to 63.7% reduction in bone marrow blast levels. Across all patients, treatment of GTB-3550 TriKE was well tolerated and no signs of cytokine release syndrome (CRS) were detected. This portion of the Phase I/II dose expansion trial is focused on determining the recommended Phase II dose, the maximum tolerated dose (MTD), optimal dose schedule, safety and tolerability of GTB-3550 TriKE administration. The Phase I safety study is expected to complete later this fall and the Company has scheduled an interim data publication for September 16-21, 2021 at the European Society for Medical Oncology Conference to be held in Paris, France.
Corporate Highlights

Announced Strategic Research Agreement with Dr. Jeffrey S. Miller of the University of Minnesota: In July 2021, GT Biopharma announced that it has entered a research agreement with Dr. Jeffrey S. Miller, associated with the University of Minnesota to further develop the Company’s proprietary TriKE technology. This agreement reinforces the clinical success that TriKE continues to demonstrate in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
Inclusion in the Russell 2000 Index: In June 2021, GT Biopharma was added to the Russel 2000 Index, signifying corporate and clinical development milestones that the Company continues to achieve. This listing enhances GT Biopharma’s visibility to a broader investment community, and increases long-term growth potential as the Company continues to achieve important clinical milestones associated with both their robust preclinical and clinical pipelines.
Announced $16M Cash Increase from Warrant Exercise Proceeds: In July 2021, the Company announced a $16M increase in cash from exercised warrant proceeds that were a part of the recent $27M financing completed in February of this year. This capital will be used to further develop the TriKE technology in both preclinical and clinical pipelines.
Conference Call

The Company will host a conference call at 8:30 a.m. EST today to provide a general business update. To join the call U.S. callers should dial 1-877-870-4263 and international callers should dial 1-412-317-0790. All participants should ask to be connected to the GT Biopharma conference call.

A live webcast of the event will be available by visiting the "Presentations" page in the Investors section of GT Biopharma’s website at www.gtbiopharma.com/news-media/presentations. A replay of the webcast will be archived for 30 days following the presentation.

About GTB-3550 TriKE

GTB-3550 is the Company’s first TriKE product candidate being initially developed for the treatment of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and other CD33+ hematologic cancers. GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of Interleukin 15 (IL-15). The natural killer (NK) cell-stimulating cytokine human IL-15 portion of the molecule provides a self-sustaining signal that activates NK cells and enhances their ability to kill. We intend to study GTB-3550 in CD33 positive leukemias such as AML, MDS and other CD33+ hematopoietic malignancies.