On June 23, 2021 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that the U.S. Food and Drug Administration (FDA) has reviewed and confirmed all comments have been addressed regarding the Company’s clinical trial protocol for the Acclaim-1 clinical trial, an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA Immunogene Therapy, in combination with AstraZeneca’s Tagrisso in patients with late-stage non-small cell lung cancer (NSCLC) whose disease progressed after treatment with Tagrisso (Press release, Genprex, JUN 23, 2021, View Source [SID1234584270]). In January 2020, Genprex received FDA Fast Track Designation for the Acclaim-1 patient population.

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In addition, the Company has engaged its first clinical site for Acclaim-1, and Genprex is continuing to work with a number of other important cancer research centers and academic institutions to select optimal study sites.

"This feedback from the FDA on our Acclaim-1 clinical trial and the engagement of our first clinical site are key milestones for Genprex," said Rodney Varner, President and Chief Executive Officer of Genprex. "We are now looking forward to opening patient enrollment in this important study of this cutting-edge investigational gene therapy to evaluate the role it can play in the fight against lung cancer, the leading cause of cancer deaths worldwide."

The Company expects the Phase 1 portion of the Acclaim-1 trial to enroll up to 18 patients at three clinical sites and for the Phase 2 portion to enroll approximately 74 patients (a 1:1 ratio of REQORSA and Tagrisso combination therapy versus Tagrisso monotherapy) at up to 15 clinical sites. The first part of the Phase 1/2 clinical trial will be a dose escalation study. The primary endpoint of the Phase 2 portion of the trial is progression-free survival, which is defined as time from randomization after first progression on Tagrisso, to first event (second progression) or death. An interim analysis will be performed at 51 events.

Genprex recently announced the Centralized Institutional Review Board (IRB) approval for the Acclaim-1 clinical trial in NSCLC. Additional information about the Acclaim-1 clinical trial can be found by visiting ClinicalTrials.gov.

On June 23, 2021 Pfizer Inc. (NYSE: PFE) reported that the first participant has been dosed in TALAPRO-3, a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial (Press release, Pfizer, JUN 23, 2021, View Source [SID1234584287]). The study will evaluate the efficacy and safety of talazoparib, an oral poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with enzalutamide, an androgen receptor inhibitor, compared with placebo plus enzalutamide in men with DNA damage response (DDR)-deficient metastatic castration-sensitive prostate cancer (mCSPC). The first patient was dosed at a site in Glendale, California.

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"The prognosis for men with advanced prostate cancer has significantly improved since the introduction of novel hormone therapies, but additional therapeutic options are needed for the approximately 25 percent of men with tumors harboring DNA damage response (DDR) gene mutations, who may have poorer outcomes," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "By combining enzalutamide, which has a proven clinical benefit in men with metastatic castration-sensitive prostate cancer, with talazoparib, our PARP inhibitor that is active in DDR-mutated cancer, we may be able to offer a new treatment option that targets the underlying genetic mechanisms associated with DDR-mutated mCSPC."

The TALAPRO-3 trial will enroll approximately 550 men with DDR-deficient mCSPC across 285 clinical trial sites in 28 countries. The primary endpoint of the study is radiographic progression-free survival (rPFS), and overall survival (OS) is a secondary endpoint. The anticipated primary completion date is late-2024.

"With the introduction of PARP inhibitors in the metastatic castration-resistant prostate cancer setting, it is important to explore how a combination approach may impact outcomes for men with metastatic castration-sensitive disease," said Neeraj Agarwal, M.D., Professor of Oncology at the University of Utah School of Medicine, Senior Director for Clinical Research Innovation at Huntsman Cancer Institute and member of the TALAPRO-3 steering committee. "It’s exciting to be at the forefront of landmark studies like TALAPRO-3, which are helping to further our understanding of how different approaches may advance care for these men."

More information about the TALAPRO-3 trial and participating sites may be found at www.clinicaltrials.gov (NCT04821622).

Talazoparib is currently approved under the brand name TALZENNA for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Selection of patients for therapy is based on an FDA-approved companion diagnostic for TALZENNA. Talazoparib is not approved for the treatment of prostate cancer. Enzalutamide is an androgen receptor inhibitor currently approved under the brand name XTANDI and is indicated for the treatment of patients with castration-resistant prostate cancer (CRPC) and mCSPC. As part of a global agreement, Pfizer and Astellas jointly commercialize XTANDI in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.

In addition to the TALAPRO-3 trial, the combination of enzalutamide plus talazoparib is being investigated in TALAPRO-2 (NCT03395197), a two-part, Phase 3, randomized, double-blind, placebo-controlled study in men with metastatic CRPC (with and without DDR defects).

About TALAPRO-3 Trial

The Phase 3, randomized, double-blind, placebo-controlled, global TALAPRO-3 trial (NCT04821622) will enroll 550 men with DDR-deficient mCSPC across approximately 285 clinical trial sites in 28 countries. In the study, participants will be randomly assigned to one of the two treatment groups and receive either talazoparib (0.50 mg once daily) in combination with enzalutamide (160 mg once daily) or placebo capsules identical to talazoparib in combination with enzalutamide. Men with moderate renal impairment at screening may be enrolled and given a lower dose of either talazoparib (0.35 mg once daily) or the placebo.

The primary endpoint of the study is radiographic progression-free survival (rPFS), which is defined as the time from the date of randomization to first objective evidence of radiographic progression or death, whichever occurs first.

About Metastatic Castration-Sensitive Prostate Cancer

Prostate cancer is considered metastatic once it has spread outside of the prostate gland to other parts of the body, such as the lymph nodes, bones, lungs, and liver.i Men are considered castration-sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels.ii The prevalence of mCSPC in the U.S. in 2020 was estimated to be just over 41,000.iii Studies have shown that DDR defects are found in 23%-27% of metastatic prostate cancers.iv,v

About talazoparib

Talazoparib is an inhibitor of PARP enzymes, which play a role in DNA response. Preclinical studies have demonstrated that talazoparib blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death. Talazoparib is being evaluated in several ongoing clinical trials in prostate cancer, as well as other novel combinations with targeted therapies in various solid tumors.

About XTANDI (enzalutamide)

XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer (mCSPC).

Prescribing Information for XTANDI and TALZENNA

Please see Full Prescribing Information for XTANDI (enzalutamide) at www.Xtandi.com.

Please see Full Prescribing Information for TALZENNA (talazoparib) at www.Talzenna.com.

About the Pfizer/Astellas Collaboration

In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE:PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize enzalutamide. The companies jointly commercialize enzalutamide in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing enzalutamide outside the United States.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.

On June 23, 2021 Tvardi reported that it launched out of Houston with the promise of finally developing the right inhibitors for the Holy Grail target of STAT3 — under the guidance of serial entrepreneur Ron DePinho and his colleague David Tweardy, a leading expert in the field. Almost three years later, they say they have the proof of concept data to keep going (Press release, Tvardi Therapeutics, JUN 23, 2021, View Source [SID1234585975]).

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It’s good enough for a $74 million Series B, a big jump from the $9 million they got in the last round and, CEO Imran Alibhai would add, a reflection of the rep his team has built.

In Phase I dose escalation studies involving patients with solid tumors who have failed all other treatments, the lead compound was shown to have downregulated the STAT3 activity of interest: blocking it from becoming phosphorylated by the receptors it typically interacts with.

"The topline news is that in over half of our patients, we’ve seen clinical benefit" in the form of tumor stabilization, shrinkage or even partial responses, he said. "That drove a lot of interest, but beyond that what’s been striking has been the safety."

He believes the secret lies in focusing on preventing the activation of STAT3, which drives the nuclear function related to disease, but not trying to remove it from the system, degrade it, or break it too much. The small window, after all, is what makes targeting STAT3 so tricky despite it being a top 5 target for cancer.

By the first half of next year, Tvardi expects to wrap up the Phase I trial and zero in on hepatocellular carcinoma in Phase II trials — while also starting to study the drug for fibrosis.

"When you think about growth and differentiation in tumors, and metastases, there’s probably three or four legs to the stool, and STAT3 is definitely one of those. Right? It is a central node," Alibhai said. "When it comes to fibrosis, there is one leg to the stool. And STAT3 modulates that pathway. And so if you could find a safe drug that actually targets STAT3, you can potentially see some really beautiful data."

Others have arrived at the same conclusion, with a small band of startups heralding new approaches such as protein degradation to target STAT3, Sanofi-partnered Kymera and Medicxi’s Janpix (now part of Centessa) among them.

For his part, Alibhai said he welcomes more options for patients and hopes Tvardi’s oral dosing small molecule treatment can set itself apart. Besides, it is not trivial to make drugs that can even get into the clinic.

"What the true test is: Can you actually get in, be safe, and be very very very targeted in the case of STAT3?" he noted. "Because there are multiple roles for STAT3 in every cell, and so we need to make sure that we’re targeting appropriately for the role that we’re interested in."

The small company is already working on a second-generation molecule that will be three to eight times more potent than the lead candidate, he said. And their new investors are in for the long game, giving them the option to either jump straight into an IPO next or raise another crossover round and, more importantly, "do something interesting."

Slate Path Capital, Palkon Capital, ArrowMark Partners and 683 Capital joined the round, with significant support from Sporos Bioventures and other existing investors.

On June 23, 2021 HUYABIO International (HUYABIO), the leader in accelerating global development of China’s pharmaceutical innovations, reported the regulatory approval for HBI-8000 monotherapy of relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATL) by the Japanese Pharmaceuticals and Medical Devices Agency (Press release, HUYA Bioscience, JUN 23, 2021, View Source [SID1234584271]).

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"Relapsed and/or refractory ATLL carries a grim prognosis with limited treatment options. Data from the registration study of HBI-8000 has demonstrated meaningful disease response despite the advanced stage of disease, and acceptable safety profile, to address an important unmet medical need in this patient population", said Dr. Atae Utsunomiya, honorary hospital director of Imamura General hospital in Japan.

The drug was approved based on data from a Phase 2b study that involved 23 patients with aggressive ATL in Japan. These patients, having few effective treatment options, all had advanced disease either refractory to or relapsed after receiving mogamulizumab. HBI-8000 40mg orally administered twice weekly resulted in disease response in a clinically meaningful proportion of patients with an acceptable safety profile.

Dr. Mireille Gillings, CEO & Executive Chair of HUYABIO said, "This first regulatory approval for our lead oncology drug, HBI-8000, is a major milestone for the Company. The durability and strong immuno- oncology properties of HBI-8000 set the stage for improved cancer treatment of both solid and liquid tumors. Synergy with PD-1/PD-L1 inhibitors hold particular promise for major solid tumor advances."

About HBI-8000

HBI-8000 is an epigenetic immunomodulator approved for the treatment of lymphoma and metastatic breast cancer in China. This oral agent targets class I histone deacetylases (HDAC) and suppresses the expression of the viral oncogene HTLV-I bZIP factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the inflammasome in ATL cells. Furthermore, HBI-8000 may induce latent viral antigen expression making ATL cells more sensitive to immune cytotoxicity targeting.

On June 23, 2021 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for blood cancers and serious hematologic diseases, reported that the results of a Phase 3 clinical study of omidubicel have been published in Blood, the official journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Gamida Cell, JUN 23, 2021, View Source [SID1234584288]). Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell transplant solution for patients with hematologic malignancies.

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The results demonstrate that transplantation with omidubicel leads to faster neutrophil and platelet recovery compared to a standard umbilical cord blood graft, and results in fewer early bacterial and viral infections and less time in the hospital.

"We are pleased that the data from this well-conducted international Phase 3 trial have been published in Blood, the highly respected, peer-reviewed journal of the American Society of Hematology (ASH) (Free ASH Whitepaper)," said Ronit Simantov, M.D., chief medical officer of Gamida Cell. "The robust results of this clinical trial have demonstrated that omidubicel could provide an important new option for patients with hematologic malignancies in need of a bone marrow transplant."

Data from this study were previously presented at the Transplantation & Cellular Therapy Meetings of the American Society of Transplantation and Cellular Therapy and Center for International Blood & Marrow Transplant Research, and most recently during the Presidential Symposium at the 47th Annual Meeting of the European Society for Blood and Marrow Transplantation. The pivotal study was an international, multi-center, randomized Phase 3 trial designed to compare the safety and efficacy of omidubicel to standard umbilical cord blood transplant in patients with high-risk hematologic malignancies undergoing a bone marrow transplant.

"Previous studies have shown that engraftment with omidubicel is durable, with some patients in the Phase 1/2 study now a decade past their transplant. The Phase 3 data reinforce omidubicel’s potential to be a new standard of care for patients who are in need of stem cell transplantation but do not have access to an appropriate matched donor," said Mitchell Horwitz, M.D., lead author of the paper and a professor of medicine at the Duke Cancer Institute.

The full Blood manuscript is available here: View Source

Details of Phase 3 Efficacy and Safety Results Shared in Blood

The intent-to-treat analysis included 125 patients aged 13–65 years with a median age of 41. Forty-four percent of the patients treated on study were non-Caucasian, a population known to be underrepresented in adult bone marrow donor registries. Patient demographics and baseline characteristics were well-balanced across the two study groups. Patients with acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome or lymphoma were enrolled at more than 30 clinical centers in the United States, Europe, Asia, and Latin America.

Gamida Cell previously reported in May 2020 that the study achieved its primary endpoint, showing that omidubicel demonstrated a statistically significant reduction in time to neutrophil engraftment, a measure of how quickly the stem cells a patient receives in a transplant are established and begin to make healthy new cells and a key milestone in a patient’s recovery from a bone marrow transplant. The median time to neutrophil engraftment was 12 days for patients randomized to omidubicel compared to 22 days for the comparator group (p<0.001).

All three secondary endpoints, details of which were first reported in December 2020, demonstrated a statistically significant improvement among patients who were randomized to omidubicel compared to patients randomized to standard cord blood graft. Platelet engraftment was significantly accelerated with omidubicel, with 55 percent of patients randomized to omidubicel achieving platelet engraftment at day 42, compared to 35 percent for the comparator (p = 0.028). Hospitalization in the first 100 days after transplant was also reduced in patients randomized to omidubicel, with a median number of days alive and out of hospital for patients randomized to omidubicel of 61 days, compared to 48 days for the comparator (p=0.005). The rate of infection was significantly reduced for patients randomized to omidubicel, with the cumulative incidence of first grade 2 or grade 3 bacterial or invasive fungal infection for patients randomized to omidubicel of 37 percent, compared to 57 percent for the comparator (p=0.027). Additional data reported in the manuscript included a comparison of infection density, or the number of infections during the first year following transplantation, which showed that the risk for grade 2 and grade 3 infections was significantly lower among recipients of omidubicel compared to control (risk ratio 0.5, p<0.001).

Data from the study relating to exploratory endpoints also support the clinical benefit demonstrated by the study’s primary and secondary endpoints. There was no statistically significant difference between the two patient groups in incidence of grade 3/4 acute GvHD (14 percent for omidubicel, 21 percent for the comparator) or all grades chronic GvHD at one year (35 percent for omidubicel, 29 percent for the comparator). Non-relapse mortality was shown to be 11 percent for patients randomized to omidubicel and 24 percent for patients randomized to the comparator (p=0.09).

These clinical data results form the basis of a Biologics License Application (BLA) that Gamida Cell plans to submit to the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2021.

About Omidubicel

Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplants for patients with hematologic malignancies (blood cancers), for which it has been granted Breakthrough Status by the FDA. Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937). The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as omidubicel. For more information on clinical trials of omidubicel, please visit www.clinicaltrials.gov.

Omidubicel is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.