On January 5, 2024 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 a review of its 2023 achievements and a preview of plans for advancing its diabetes and oncology gene therapy programs in 2024 (Press release, Genprex, JAN 5, 2024, View Source [SID1234639011]).

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"We are very proud of what we accomplished in 2023, particularly with the successful completion of the Phase 1 portion of our Acclaim-1 clinical trial in lung cancer," said Rodney Varner, Chairman, President and Chief Executive Officer at Genprex. "In 2023, we also received a third Fast Track Designation for Reqorsa Immunogene Therapy from the U.S. Food and Drug Administration, this time in combination with Tecentriq for the treatment of small cell lung cancer, and REQORSA was also granted Orphan Drug Designation for the treatment of small cell lung cancer. We believe these designations underscore and further validate the potential of REQORSA. Our accomplishments in 2023, which also include process improvements in our manufacturing operations and securing new supplies of REQORSA, sets the foundation for a strong 2024."

Oncology Gene Therapy Platform

Genprex’s oncology program utilizes its systemic, non-viral Oncoprex Nanoparticle Delivery System which encapsulates the gene-expressing plasmids using lipid nanoparticles. The resultant product is administered intravenously, where it is taken up by tumor cells that then express tumor suppressor proteins that were deficient in the tumor. The Company’s lead product candidate, REQORSA (quaratusugene ozeplasmid), is being evaluated in three clinical trials as a treatment for non-small cell lung cancer ("NSCLC") and small cell lung cancer ("SCLC"), andeach of the three lung cancer clinical programs has received a Fast Track Designation from the FDA for the treatment of that patient population.

REQORSA has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for apoptosis (programmed cell death) in cancer cells, and modulates the immune response against cancer cells. In early studies, REQORSA has been shown to be complementary with targeted drugs and immunotherapies. Genprex’s strategy is to develop REQORSA in combination with currently approved therapies and believes that REQORSA’s unique attributes position it to provide treatments that improve on these current therapies for patients with NSCLC, SCLC, and possibly other cancers.

Important events of the year included:

In April, at the 2023 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2023), Genprex collaborators presented preclinincal gene therapy data with NPRL2, another tumor suppressor gene, that further validates the ONCOPREX Nanoparticle Delivery System as a platform
In October, Genprex hosted a Key Opinion Leader virtual event, "Bringing Gene Therapy to the Fight Against Lung Cancers" which discussed the use of gene therapies, including REQORSA, in the fight against lung cancer
In December, Genprex completed the successful production of a new batch of REQORSA thereby securing REQORSA supply for its Acclaim clinical studies
Collaborators submitted abstracts in 2023 and are expecting to present data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Meeting in April 2024
Acclaim-1: 

The Acclaim-1 study is a Phase 1/2 clinical trial that has three portions – a Phase 1 dose escalation which has been completed, a Phase 2a expansion, and a Phase 2b randomized portion. Acclaim-1 uses a combination of REQORSA and AstraZeneca’s Tagrisso in patients with late-stage NSCLC that has activating epidermal growth factor receptor mutations and progression after treatment with Tagrisso. This novel approach to targeting lung cancer has demonstrated a strong safety profile with early signs of efficacy.

In May, Genprex completed the Phase 1 portion of the Acclaim-1 clinical trial and reported encouraging results. The Acclaim-1 Phase 1 study had no Dose Limiting Toxicities and results established a Phase 2 Recommended Dose, as well as provided data showing efficacy of REQORSA in combination with Tagrisso
In May, after completion of the Phase 1 portion of the Acclaim-1 trial, the Safety Review Committee ("SRC") approved advancement from the Phase 1 dose escalation portion of the trial to the Phase 2a expansion portion of the trial
In October, clinical collaborators presented a poster presentation at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) showing the Phase 1 results of the Acclaim-1 study
In January 2024, Genprex expects to open the Phase 2a expansion portion of the Acclaim-1 study for enrollment
Genprex expects to complete the enrollment of 19 patients in each cohort of the Phase 2a expansion portion of the study by the end of 2024
Acclaim-2:

The Acclaim-2 study is a Phase 1/2 clinical trial that has three portions – a Phase 1 dose escalation portion, a Phase 2a expansion portion, and a Phase 2b randomized portion.  The Acclaim-2 trial uses a combination of REQORSA and Merck & Co.’s Keytruda in patients with late-stage NSCLC whose disease has progressed after treatment with Keytruda. Patients are treated at the 0.06 mg/kg dose level in the first cohort of patients and, subject to the Acclaim-2 SRC approval, will be treated at successive dose levels of 0.09 mg/kg and 0.12 mg/kg.

Expanding on the previously granted patents in the U.S., Japan, Mexico and Russia, Genprex was granted patents in Australia, Chile and China to cover the use of REQORSA in combination with immune checkpoint inhibtors, e.g., PD1 and PDL1 inhibitors. These patents are applicable to Genprex’s Acclaim-2 and Acclaim-3 clinical trials.
In the second half of 2024, Genprex expects to complete enrollment in the Phase 1 dose escalation portion of the Acclaim-2 study
Acclaim-3:

The Acclaim-3 study has two portions – a Phase 1 dose escalation portion and a Phase 2 expansion portion. In November 2022 Genprex filed with the FDA the protocol for the Phase 1/2 Acclaim-3 clinical trial using a combination of REQORSA and Genentech, Inc.’s Tecentriq as maintenance therapy for patients with extensive stage small cell lung cancer ("ES-SCLC") who develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. Patients will be treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced.

In June, the FDA granted Fast Track Designation for the Acclaim-3 treatment combination of REQORSA and Tecentriq as maintenance therapy in patients with ES-SCLC who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment
In August, the FDA granted Orphan Drug Designation to REQORSA for the treatment of SCLC
In January 2024, Genprex expects to open the Phase 1 portion of the Acclaim-3 study for enrollment, and expects to complete the Phase 1 portion of the study by the second half of 2024
In the second half of 2024, Genprex expects to start the Phase 2 portion of the Acclaim-3 study
Diabetes Gene Therapy Platform

Genprex’s diabetes gene therapy approach is comprised of an infusion process that uses an adeno-associated virus ("AAV") vector to deliver Pdx1 and MafA genes directly to the pancreas. In models of Type 1 diabetes, GPX-002 transforms alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body’s immune system. In a similar approach, GPX-003 for Type 2 diabetes, where autoimmunity is not at play, is believed to rejuvenate and replenish exhausted beta cells. Genprex has exclusively licensed from the University of Pittsburgh of the Commonwealth System of Higher Education ("University of Pittsburgh") multiple technologies relating to the development of a gene therapy product for each of Type 1 and Type 2 diabetes. In October 2023, Genprex entered into a one-year extension to the August 2022 sponsored research agreement with the University of Pittsburgh. The extension includes a revised research plan to encompass the Company’s most recent technologies to which Genprex acquired exclusive rights from the University of Pittsburgh in July 2023. These include a MafB promoter to drive expression of the Pdx1 and MafA transcription factors that can potentially be used for both Type 1 and Type 2 diabetes. This research is expected to be initially conducted in a Type 1 animal model.

In February, Genprex’s research collaborators at the University of Pittsburgh presented preclinical data in a NHP model of Type 1 diabetes highlighting the therapeutic potential of GPX-002. These data, presented during an oral presentation at the 16th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2023), showed statistically significant decreases in insulin requirements, increased c-peptide levels and improved glucose tolerance compared to baseline.
In April, the Company hosted a Key Opinion Leader virtual event, "Novel Gene Therapy to Treat Type 1 Diabetes," which discussed preclinical data reported at ATTD 2023 supporting gene therapy to treat Ttype 1 diabetes
Finalized the components of the diabetes construct to take forward for nonclinical studies
In December, Genprex submitted a request to meet with the FDA to obtain their guidance on the nonclinical studies needed to file an Investigational New Drug application and initiate first-in-human studies. As a result of the FDA’s response, the Company will continue with its planned additional nonclinical studies before requesting regulatory guidance in 2024 for the IND-enabling studies.

On January 5, 2024 Genprex presented its corporate presentation (Presentation, Genprex, JAN 5, 2024, View Source [SID1234639009]).

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On January 5, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported program updates and upcoming 2024 milestones (Press release, Elevation Oncology, JAN 5, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-announces-program-updates-and-upcoming-2024-milestones [SID1234639008]).

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"Our vision is to leverage our ADC and oncology drug development expertise to deliver innovative, selective cancer therapies to millions of patients with significant unmet needs. In 2023, we made meaningful progress toward this goal, focusing our resources on advancing EO-3021, our anti-Claudin 18.2 ADC therapy," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "As evidenced by initial clinical data presented by our partner, we believe EO-3021 represents a highly differentiated, potentially best-in-class molecule, able to deliver better tolerability and improved anti-tumor activity to patients with tumors expressing varying levels of Claudin 18.2. We look forward to sharing an update from our ongoing trial in mid-2024."

Mr. Ferra continued, "We are also expanding our development program to realize the full potential of anti-Claudin 18.2-targeting as a therapeutic approach. To expand on available treatment options and optimize outcomes, particularly in the gastric cancer setting, we plan to evaluate EO-3021 in combination with both immunotherapy and targeted agents and will share details on our planned Phase 1 combination study in the first half of 2024. In addition, we are excited to reveal that our second program, an ADC targeting HER3, continues to advance and we expect to nominate a development candidate later this year."

Program Updates and Upcoming Milestones

EO-3021: Elevation Oncology is advancing EO-3021, a differentiated antibody drug conjugate (ADC) for the treatment of patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

Single Agent:

Elevation Oncology plans to provide an update from its ongoing Phase 1 trial in mid-2024, with additional data expected in the first half of 2025.
In June 2023, Elevation Oncology’s partner, CSPC Pharmaceutical Group Limited, presented initial clinical data for SYSA1801 (EO-3021) from their ongoing Phase 1 dose escalation and expansion study in China. Initial data showed promising signs of efficacy, including a 47.1% overall response rate (ORR) in patients with resistant/refractory gastric cancer expressing Claudin 18.2, with a well-tolerated safety profile.
In August 2023, Elevation Oncology began enrolling patients in an open-label, multi-center, dose escalation and expansion Phase 1 clinical trial (NCT05980416), designed to evaluate the safety, tolerability and preliminary anti-tumor activity of EO-3021.
Combination:

Elevation Oncology plans to expand its clinical development program to evaluate EO-3021 in combination. The Company believes a combination approach has the potential to offer optimal outcomes to patients, particularly in the gastric cancer setting, and plans to explore combination strategies with both immunotherapy and targeted agents. Elevation Oncology expects to share details on its planned Phase 1 combination study in the first half of 2024.
HER3-ADC: Elevation Oncology’s second program is a differentiated HER3-targeting ADC. HER3 is a well-validated ADC target, which is overexpressed across solid tumors and often associated with poor outcomes. There are currently no HER3-targeted ADC agents approved for the treatment of cancer.

Elevation Oncology is currently evaluating its HER3-ADC program and plans to nominate a development candidate in 2024.
Financial Guidance

Elevation Oncology expects that its cash, cash equivalents and marketable securities as of September 30, 2023, will be sufficient to fund its current operations into the second half of 2025.

About EO-3021

EO-3021 (also known as SYSA1801) is a differentiated, clinical-stage antibody drug conjugate (ADC) with best-in-class potential comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2. EO-3021 is site-specifically conjugated to the monomethyl auristatin E (MMAE) payload via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformations, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 study (NCT05980416) in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

On January 5, 2024 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported that Nature Medicine has published results from a circulating tumor DNA (ctDNA) analysis of the INTRIGUE Phase 3 study of QINLOCK (ripretinib) in GIST patients with mutations in KIT exon 11 and 17/18 only previously treated with imatinib (Press release, Deciphera Pharmaceuticals, JAN 5, 2024, View Source [SID1234639007]).

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The article, titled "Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial" is now available online and will be published in a future print issue of Nature Medicine.

"The results published in Nature Medicine provide compelling evidence that QINLOCK may provide progression-free and overall survival benefit to second-line (2L) GIST patients in whom a liquid biopsy reveals primary KIT exon 11 mutations plus secondary mutations restricted to KIT exons 17 and 18. It is the first test that measures heterogeneity of resistance and may allow for a more optimized and targeted treatment plan for people living with this disease," said Sebastian Bauer, M.D., Medical Oncologist at the West German Cancer Center in Essen and senior author of the manuscript. "This analysis is leading us to consider a new approach in GIST treatment using sensitive and minimally invasive blood tests to identify the specific secondary mutational profile for individual patients in order to tailor their therapy based on the differential activity of QINLOCK and sunitinib seen in the INTRIGUE subgroup analysis."

"In second-line GIST patients with KIT exon 11 + 17/18 mutations only, treatment with QINLOCK resulted in a 78% reduction in the risk of disease progression and a 66% reduction in the risk of death compared to sunitinib, representing a substantial clinical benefit for these patients," said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera. "Our ongoing INSIGHT pivotal Phase 3 study is designed to confirm the exceptional efficacy we observed in this exploratory analysis from INTRIGUE. The INSIGHT study is now open at multiple sites and we are committed to enrolling the study as quickly as possible."

INTRIGUE is an international, multi-center study conducted in 122 active sites across 22 countries, where 453 patients in the all patient intent-to-treat population (AP-ITT) with second-line GIST were randomized to receive ripretinib (n=226) or sunitinib (n=227).

In the AP-ITT population, QINLOCK demonstrated similar efficacy with a median progression-free survival (PFS) of 8.0 months versus 8.3 months for sunitinib (HR 1.05, nominal p=0.72). There were fewer patients with Grade 3-4 drug-related treatment emergent adverse events (TEAE) with QINLOCK (26.5%) compared with sunitinib (55.2%). Based on the primary results from the INTRIGUE study, QINLOCK was included in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (version 1.2023) as the preferred second-line regimen for patients with advanced GIST who are intolerant to sunitinib.

A prespecified exploratory objective in INTRIGUE was to evaluate anti-tumor efficacy of QINLOCK according to baseline KIT primary and secondary mutation status. Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing liquid biopsy assay in patients for whom evaluable samples were available (n=362) out of whom 280 patients had detectable ctDNA. In patients with a detectable KIT exon 11 primary mutation (n=157), 52 patients also had mutations in KIT exon 17/18 only and 41 had mutations in KIT exon 13/14 only.

Patients with mutations in KIT exon 11 and 17/18 only had improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) with QINLOCK versus sunitinib while patients with mutations in KIT exon 11 and 13/14 only had improved PFS, ORR, and OS with sunitinib compared to QINLOCK.

Summary of INTRIGUE Efficacy Results of ctDNA Analysis for Patients with Mutations in KIT Exon 11 and 17/18 Only

Ripretinib

(n=27)

Sunitinib

(n=25)

Hazard
Ratio/Response
Difference
(95% CI)

Median Progression-Free Survival (1)

14.2 months

1.5 months

0.22 (0.11, 0.44), nominal p value <0.0001

Objective Response Rate (1)

44.4%

0%

44.4% (23.0%, 62.7%)

nominal p value = 0.0001

Overall Survival (2)

Not Estimable

17.5 months

0.34 (0.15, 0.76), nominal p value = 0.0061

Notes: (1) Data cutoff as of September 1, 2021; (2) Data cutoff as of September 1, 2022.

The subgroup safety profile was consistent with the primary analysis in the AP-ITT population and demonstrated a more favorable safety profile for QINLOCK compared with sunitinib with fewer patients experiencing Grade 3-4 drug-related TEAEs (KIT exon 11 and 17/18 only: 33.3% for QINLOCK versus 50.0% for sunitinib).

About the INSIGHT Study

The INSIGHT Phase 3 clinical study is a randomized, global, multicenter, open-label study to evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients with GIST previously treated with imatinib with mutations in KIT exon 11 and 17/18 only (excluding patients with mutations in KIT exons 9, 13, or 14). In the study, 54 patients will be randomized 2:1 to either QINLOCK 150 mg once daily or sunitinib 50 mg once daily for four weeks followed by two weeks without sunitinib. The primary endpoint is PFS as determined by independent radiologic review using modified RECIST 1.1 criteria. Secondary endpoints include ORR as determined by independent radiologic review using modified RECIST 1.1 criteria and OS.

About the INTRIGUE Study

The INTRIGUE Phase 3 clinical study is a randomized, global, multicenter, open-label study to evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients with GIST previously treated with imatinib. In the study, 453 patients were randomized 1:1 to either QINLOCK 150 mg once daily or sunitinib 50 mg once daily for four weeks followed by two weeks without sunitinib. As previously reported, the study did not achieve the primary efficacy endpoint of PFS as determined by independent radiologic review using modified RECIST 1.1 criteria. The statistical analysis plan included a hierarchical testing sequence that included testing patients with a KIT exon 11 primary mutation and then in the all patient intent-to-treat (AP-ITT) population. In patients with a KIT exon 11 primary mutation (n=327), QINLOCK demonstrated a median PFS of 8.3 months compared to 7.0 months for the sunitinib arm (HR 0.88, p=0.360). Although not formally tested due to the rules of the hierarchical testing sequence, in the AP-ITT population QINLOCK demonstrated a median PFS of 8.0 months compared to 8.3 months for the sunitinib arm (HR 1.05, nominal p=0.72). QINLOCK was generally well tolerated. Fewer patients in the QINLOCK arm experienced Grade 3-4 treatment-emergent adverse events compared to sunitinib (41.3% vs. 65.6%). Similarly, there were fewer patients with Grade 3-4 drug-related TEAEs with ripretinib (26.5%) compared with sunitinib (55.2%).

On January 5, 2024 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that on January 2, 2024, the independent Compensation Committee of the Board of Directors of Curis approved the grant of inducement stock options to purchase a total of 5,800 shares of Curis common stock to a new employee, with a grant date of January 2, 2024 (the "Q1 2024 Inducement Grant") (Press release, Curis, JAN 5, 2024, View Source [SID1234639006]).

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The Q1 2024 Inducement Grant has an exercise price per share equal to the closing price of the Company’s common stock on January 2, 2024. The stock option has a 10 year term and vests over four years, with 25% of the original number of shares underlying the award vesting on the first anniversary of the employee’s date of hire and an additional 6.25% of the original number of shares underlying the award vesting on each successive three-month period thereafter, subject to the employee’s continued service with the Company through the respective vesting dates. The stock option was granted as an inducement equity award outside of the Company’s Fourth Amended and Restated 2010 Stock Incentive Plan and was made as an inducement material to the employee’s acceptance of employment with the Company.