On August 13, 2021 Leap Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported financial results for the second quarter ended June 30, 2021 and provided upcoming company milestones (Press release, Leap Therapeutics, AUG 13, 2021, View Source [SID1234586549]).

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"In the first half of the year, we made significant clinical progress in the DisTinGuish study of DKN-01 in combination with BeiGene’s tislelizumab, as we completed enrollment in the first-line patient cohort," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "We look forward to presenting initial data from the study in September, which we believe will show the important potential role DKN-01 can play for first-line gastric cancer patients, particularly those whose tumors express high levels of DKK1 where a great unmet medical need remains unaddressed."

Key DKN-01 2021 Clinical Milestones

DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways, which play an important role in tumor cell signaling and in mediating an immuno-suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells.

Leap made substantial progress with the clinical development of DKN-01 during the first half of 2021 and has an important clinical milestone ahead this quarter:

Completion of Enrollment in First-Line Cohort in the DisTinGuish Study of DKN-01 plus Tislelizumab and Chemotherapy in Gastric Cancer. The Company announced the completion of enrollment for the first-line patient cohort in the DisTinGuish study (NCT04363801), a Phase 2a, open-label, clinical trial evaluating DKN-01 in combination with tislelizumab, BeiGene Ltd.’s (BeiGene) anti-PD-1 antibody, with or without chemotherapy, in patients with gastric or gastroesophageal junction cancer (G/GEJ). The study, which is being conducted in two parts in the United States and the Republic of Korea, enrolled 25 patients with first-line G/GEJ cancer and is expected to enroll up to 48 patients with second-line G/GEJ cancer whose tumors express high levels of DKK1. Leap is conducting this study as part of an exclusive option and license agreement with BeiGene for the development of DKN-01 in Asia (excluding Japan), Australia, and New Zealand.

Initial Data from the DisTinGuish Study of DKN-01 Plus Tislelizumab and Chemotherapy to be Presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021. The Company will be presenting initial data from the cohort of 25 first-line G/GEJ cancer patients treated with DKN-01 in combination with tiselizumab and chemotherapy at the ESMO (Free ESMO Whitepaper) Congress 2021, being held virtually on September 16-21, 2021. Leap plans to host a conference call on Friday, September 17, 2021 to further discuss the data.

Selected Second Quarter 2021 Financial Results

Net loss was $9.5 million for the second quarter 2021, compared to $6.5 million for the same period in 2020.

License revenues were $0.4 million for each of the second quarter 2021 and the same period in 2020, and relate to the exclusive option and license agreement with BeiGene for the development and commercialization of DKN-01 in Asia (excluding Japan), Australia, and New Zealand.

Research and development expenses were $7.2 million for the second quarter 2021, compared to $5.4 million for the same period in 2020. The increase of $1.8 million in research and development expenses was primarily due to an increase of $0.8 million in payroll and other related expenses due to an increase in headcount of research and development full-time employees, an increase of $0.6 million in manufacturing costs related to clinical trial material due to timing of manufacturing campaigns, an increase of $0.3 million in clinical trial costs due to timing of patient enrollment, and an increase of $0.1 million in stock based compensation expense due to new stock options granted to research and development full-time employees in 2021.

General and administrative expenses were $2.8 million for the second quarter 2021, compared to $2.5 million for the second quarter 2020. The increase of $0.3 million in general and administrative expenses was due to a $0.2 million increase in payroll and other related expenses, a $0.2 million increase in stock-based compensation expense due to new stock options granted to general and administrative full-time employees in 2021, and a $0.1 million increase in insurance costs primarily related to an increase in our directors and officers insurance. These increases were partially offset by a $0.2 million decrease in professional fees primarily due to lower recruiting and information technology costs.

Cash and cash equivalents totaled $35.7 million at June 30, 2021. Research and development incentive receivables totaled $0.2 million at June 30, 2021.

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 [SID1234586567]). 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 PMV Pharmaceuticals, Inc. (Nasdaq: PMVP), a clinical-stage oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies designed to target p53 mutants, reported financial results for the second quarter ended June 30, 2021 and provided corporate highlights (Press release, PMV Pharma, AUG 13, 2021, View Source [SID1234586519]).

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"We are encouraged by our execution in the clinic, with steady progress in the ongoing Phase 1/2 trial of PC14586," said David Mack, Ph.D., President and Chief Executive Officer of PMV Pharma. "We believe PC14586, our first-in-class, tumor agnostic, p53 Y220C reactivator has the potential to transform outcomes for cancer patients. Furthermore, our strong balance sheet leaves us well positioned to continue to translate our deep scientific expertise to deliver benefits to patients."

Corporate Highlights:

Continued enrollment in the Phase 1 portion of a Phase 1/2 clinical trial of PC14586, the Company’s first-in-class, tumor-agnostic, investigational small molecule p53 Y220C reactivator, in patients with advanced solid tumors that have a p53 Y220C mutation (NCT04585750).
Activated twelve clinical trial sites in the United States, consisting of leading oncology centers.
Commenced construction of new corporate headquarters and state-of-the-art laboratories in Princeton, New Jersey.
Second Quarter 2021 Financial Results

PMV Pharma ended the second quarter with $339.0 million in cash, cash equivalents, and marketable securities, compared to $361.4 million as of December 31, 2020. Net cash used in operations was $22.0 million for the six months ended June 30, 2021, compared to $15.0 million for the six months ended June 30, 2020.
Net loss for the six months ended June 30, 2021 was $24.5 million compared to $15.2 million for the six months ended June 30, 2020.
Research and development (R&D) expenses were $15.2 million for the six months ended June 30, 2021 compared to $11.8 million for the six months ended June 30, 2020. The increase in R&D expenses was primarily due to increased headcount and clinical expenses related to development of PC14586, the Company’s lead drug candidate.
General and administrative (G&A) expenses were $9.6 million for the six months ended June 30, 2021 compared to $4.0 million for the six months ended June 30, 2020. The increase in G&A expenses was primarily due to costs relating to building the infrastructure necessary to operate as a public company.
About p53

p53 plays a pivotal role in preventing abnormal cells from becoming a tumor by inducing programmed cell death. Mutant p53 takes on oncogenic properties that endow cancer cells with a growth advantage and resistance to anti-cancer therapy. The p53 Y220C mutation is associated with many cancers, including but not limited to breast, non-small cell lung cancer, colorectal, pancreatic, and ovarian cancers.

About PC14586

PC14586 is a first-in-class, small molecule, p53 reactivator designed to selectively bind to the crevice present in the p53 Y220C mutant protein, hence, restoring the wild-type, or normal, p53 protein structure and tumor suppressing function. PC14586 is being developed for the treatment of patients with locally advanced or metastatic solid tumors that have the p53 Y220C mutation and has been granted Fast Track designation by the U.S. FDA.

On August 13, 2021 Protalix BioTherapeutics, Inc. (NYSE American:PLX) (TASE:PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported the entry into definitive agreements (the "Exchange Agreements") relating to exchanges (the "Exchanges") of an aggregate of $54.65 million principal amount of the Company’s outstanding 7.50% Senior Secured Convertible Notes due 2021 (the "Existing Notes") for an aggregate of $28.75 million principal amount of newly issued 7.50% Senior Secured Convertible Notes due 2024 (the "Exchange Notes"), $25.90 million in cash and accrued and unpaid interest through the closing date (Press release, Protalix, AUG 13, 2021, View Source [SID1234586550]). The Exchanges are expected to close as soon as practicable, subject to satisfaction of certain closing conditions. Following the closing of the Exchanges, the Company expects that $3.27 million aggregate principal amount of the Existing Notes will remain outstanding.

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"The exchange of the notes underscores Protalix’s commitment to addressing our capital structure while continuing development of our pegunigalsidase alfa program and our early pipeline," said Dror Bashan, Protalix’s President and Chief Executive Officer. "We believe that the participation of so many of our institutional note holders, including funds managed by Highbridge Capital Management, LLC, UBS O’Connor LLC, Citigroup Global Markets, Whitebox Advisors, and Tulip Capital, is a telling vote of confidence in Protalix."

Like the Existing Notes and at equal priority, the Exchange Notes will be secured by perfected liens on all of the material assets of the Company and its subsidiaries. Interest on the Exchange Notes will be payable semi-annually at a rate of 7.50% per annum. The Exchange Notes will mature three years after issuance, unless earlier purchased, converted, exchanged or redeemed, and will be guaranteed by the Company’s subsidiaries.

Holders may require the Company to repurchase their Exchange Notes upon the occurrence of certain events that constitute a fundamental change under the indenture that will govern the Exchange Notes (the "Indenture") at a purchase price equal to the principal amount thereof plus accrued and unpaid interest to, but excluding, the fundamental change purchase date.

Holders may convert their Exchange Notes at any time prior to the close of business on the business day immediately preceding the stated maturity date of the Exchange Notes. Upon conversion, the Company may, at its election, deliver shares of the Company’s common stock ("Common Stock"), cash or a combination of shares of Common Stock and cash based on the applicable conversion rate. However, until the Company obtains stockholder approval to issue additional shares of Common Stock upon conversion of the Exchange Notes, the Company will be required to settle at least a portion of its conversion obligation in cash. The Company intends to seek stockholder approval promptly in order to be able to settle conversions of the Exchange Notes in Common Stock.

The initial conversion rate will be based on a 32.5% premium to the closing price of the Common Stock on the NYSE American at the close of trading on August 13, 2021.

The Indenture includes covenants customary for instruments of this type, including, without limitation, restrictions on the Company’s ability to incur additional indebtedness, create liens on its properties, pay dividends and make restricted payments or certain investments, and also requires the Company to apply a portion of the proceeds from certain asset sales or licensing arrangements to repay the Exchange Notes, in each case subject to certain exceptions.

"This exchange transaction allows us to continue to advance our lead drug candidate, PRX-102, towards approval and to progress our early stage pipeline candidates," said Eyal Rubin, Protalix’s Sr. Vice President and Chief Financial Officer.

This announcement is neither an offer to sell nor a solicitation of an offer to buy any of these securities and shall not constitute an offer, solicitation, or sale in any jurisdiction in which such offer, solicitation, or sale is unlawful. The offer and sale of the Exchange Notes and the shares of Common Stock issuable upon conversion of the Exchange Notes, if any, will not be registered under the Securities Act of 1933 or any state securities laws, and unless so registered, the Exchange Notes and such shares may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Securities Act of 1933 and applicable state laws.

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.