On December 14, 2022 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products issued a positive opinion on Panbela’s application for orphan designation of ivospemin (SBP-101) in combination with gemcitabine and nabPaclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (PDA) (Press release, Panbela Therapeutics, DEC 14, 2022, View Source;utm_medium=rss&utm_campaign=panbela-receives-positive-ema-opinion-on-orphan-designation-for-ivospemin-sbp-101-in-combination-with-gemcitabine-and-nab-paclitaxel-in-patients-with-metastatic-pancreatic-ductal-adenocarcinoma [SID1234625267]). Previously, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to SBP-101.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to receive a notification of positive opinion for orphan drug designation from EMA’s Committee Orphan Medicinal Products following its December plenary meeting," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. "The opinion is timely, as we only a few weeks ago announced first patients enrolled in Europe in our ASPIRE trial. We continue to advance the global clinical trial, as we aim for interim analysis in early 2024."

Orphan drug designation in the European Union (EU) is granted by the European Commission based on a positive opinion issued by the EMA Committee for Orphan Medicinal Products. The EMA’s orphan designation is available to companies developing treatments for life-threatening or chronically debilitating conditions that affect fewer than five in 10,000 persons in the EU. Medicines that meet the EMA’s orphan designation criteria qualify for financial and regulatory incentives, including a 10-year period of marketing exclusivity in the EU after product approval, protocol assistance from the EMA at reduced fees during the product development phase and access to centralized marketing authorization.

Panbela is continuing to focus on site initiation and enrollment to ultimately deliver a more effective treatment for pancreatic cancer, a deadly disease with few treatment options. The Company expects that a significant number of global sites will be open by year-end with the full complement of sites open by early-to-mid 2023.

About our Pipeline

The pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention and ovarian cancer. The combined development programs have a steady cadence of catalysts with programs ranging from pre-clinical to registration studies.

SBP-101

Ivospemin Ivospemin is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. It has shown signals of tumor growth inhibition in clinical studies of metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months and an objective response rate (ORR) of 48%, both exceeding what is typical for the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, ivospemin has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the previous Panbela-sponsored clinical trials provide support for continued evaluation of ivospemin in the ASPIRE trial. For more information, please visit View Source

Flynpovi

Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increase polyamine export and catabolism. In a Phase 3 clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase 3 trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), Flynpovi showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP.

CPP-1X

CPP-1X (eflornithine) is being developed as a single agent tablet or high dose power sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase 1 or Phase 2 investigatorinitiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity.

On December 14, 2022 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that the European Commission (EC) has designated upifitamab rilsodotin (UpRi) as an orphan medicinal product for the treatment of ovarian cancer (Press release, Mersana Therapeutics, DEC 14, 2022, View Source [SID1234625266]). UpRi is Mersana’s first-in-class NaPi2b-targeting ADC with a novel scaffold-linker-payload that is designed to enable a high drug-to-antibody ratio and controlled bystander effect.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Receiving this orphan designation in the European Union is an important regulatory milestone for Mersana as we seek to expedite UpRi’s global development," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "This designation reinforces the unmet needs that patients with ovarian cancer continue to face today. We look forward to advancing our ongoing clinical trials, which aim to establish UpRi as a foundational medicine in ovarian cancer."

The European Commission designates drugs as orphan medicinal products based on positive opinions adopted by the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP). Orphan designations are granted for potential treatments for rare diseases that are life-threatening or chronically debilitating that affect fewer than five in 10,000 people across the European Union. Medicines designated as orphan medicinal products by the EMA may qualify for financial and regulatory incentives, including protocol assistance at reduced fees during product development, access to centralized marketing authorization and 10 years of marketing exclusivity in the European Union after product approval.

On December 14, 2022 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage drug development company focused on DNA-based immunotherapy and next-generation vaccines, reported that the Compensation Committee of the Company’s Board of Directors approved the grant of (i) inducement stock options (the "Inducement Option Grants") to purchase a total of 19,000 shares of common stock and (ii) restricted stock grants (the "Inducement Stock Grants") totaling 4,000 shares of common stock as a material inducement to the employment to four individuals hired by IMUNON during the fourth quarter of 2022 (Press release, IMUNON, DEC 14, 2022, View Source [SID1234625265]). The equity awards were approved in accordance with Nasdaq Listing Rule 5635 (c)(4).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Inducement Option Grants have an exercise price per share equal to $1.40 which is equal to the closing price of IMUNON’s common stock as reported by Nasdaq on December 13, 2022. The Inducement Option Grants vest in thirds over three years with the vesting starting on the one-year anniversary of each employee’s first day of employment with the Company and thereafter vest in two additional installments so all Inducement Option Grants will be fully vested and exercisable as of December 13, 2025, subject to each employee’s continued service relationship with the Company on each such date. Each Inducement Option Grant has a ten-year term.

Each of the Inducement Stock Grants will vest on the one-year anniversary of each employee’s first date of employment with the Company and are subject to each such employee’s continued service relationship with the Company on such vesting date.

On December 14, 2022 Immix Biopharma, Inc. (Nasdaq: IMMX) ("ImmixBio", "Company", "We" or "Us"), a biopharmaceutical company pioneering Tissue-Specific Therapeutics (TSTx)TM targeting oncology and immuno-dysregulated diseases, reported that it has in-licensed BCMA-targeted next-generation CAR-T therapy NXC-201 (formerly HBI0101) with 85% overall response rate (ORR) and 71% complete response/stringent complete response (CR/sCR) at the therapeutic dose from the first 20 patients in an ongoing phase 1b relapsed/refractory multiple myeloma ongoing clinical trial as of June 27, 2022 data cutoff with a median of 6 (range, 3-13) prior lines of therapy (Press release, Immix Biopharma, DEC 14, 2022, View Source [SID1234625263]). NXC-201 also produced 100% ORR and 100% organ response rate in 4 relapsed/refractory AL Amyloidosis patients. In addition, zero neurotoxicity of any grade was observed and zero events of immune effector cell-associated neurotoxicity syndrome (ICANs) were observed with NXC-201 treatment as of the June 27, 2022 data cutoff. These data were published in Haematologica View Source (multiple myeloma) and Clinical Cancer Research View Source (AL amyloidosis). Immix Biopharma has formed a wholly-owned subsidiary, Nexcella, Inc., to develop and potentially commercialize NXC-201.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Low-grade (grade 1/2) CRS duration of median 2 days with median onset of 1-day post-dosing (range, 1-5 days) at therapeutic dose in relapsed/refractory multiple myeloma points to NXC-201 potentially becoming the first and only out-patient CAR-T for Multiple Myeloma, AL Amyloidosis and other BCMA-positive malignancies. The formation of Nexcella, Inc is expected to have a minimal impact on Immix Biopharma’s financial position, as Nexcella, Inc is expected to be an independently financed company.

ThinkEquity LLC acted as advisor to Immix Biopharma in this transaction.

"We are thrilled to share that we have secured exclusive rights to NXC-201, a next generation BCMA CAR-T therapy whose 85% ORR and 71% CR rate in heavily pretreated multiple myeloma patients in the ongoing Phase 1 trial are compelling," said Ilya Rachman, MD PhD, CEO of Immix Biopharma. "Additionally, encouraged by the 100% complete response rate and 100% organ response rate in AL Amyloidosis, we are planning to enroll additional patients to validate these findings."

"Considering its short 2-day median CRS duration, occurring within a median 1-day post-dosing, we look forward to exploring outpatient administration of NXC-201," added Gabriel Morris, CFO of Immix Biopharma.

About NEXICART-1

NEXICART-1 (NCT04720313) is an ongoing Phase 1b/2, open-label study evaluating the safety and efficacy of NXC-201 (formerly HBI10101), in adults with relapsed or refractory multiple myeloma, all of which as of June 27, 2022 were triple-class refractory (to at least 1 immunomodulatory drug, 1 proteasome inhibitor and 1 anti-CD38 antibody).

The primary objective of the Phase 1b portion of the study, is to characterize the safety and confirm the Maximally Tolerated Dose (MTD) and Phase 2 dose of NXC-201. The Phase 2 portion of the study will evaluate the efficacy and safety of NXC-201 with endpoints of overall survival, progression-free survival and response rates according to International Myeloma Working Group (IMWG) Uniform Response Criteria.

About NXC-201

NXC-201 (formerly HBI10101) is a BCMA-targeted investigational chimeric antigen receptor T (CAR-T) cell therapy that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and amyloidosis. The design consists of a structurally differentiated CAR-T, with our proprietary BCMA-targeting CAR, which has demonstrated reduced toxicity in NEXICART-1, supporting investigating NXC-201 as an outpatient therapy.

About Multiple Myeloma
Multiple myeloma ("MM") is an incurable blood cancer of plasma cells that starts in the bone marrow and is characterized by an excessive proliferation of these cells. Despite initial remission, unfortunately, most patients are likely to relapse. There are 34,470 patients in the United States diagnosed with MM each year. Prognosis for patients who do not respond to or relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents remains poor.

On December 14, 2022 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 Safety Review Committee (SRC) has approved continuation to the third and final cohort in the dose escalation Phase 1 portion of the Acclaim-1 Phase 1/2 clinical trial of REQORSA in combination with Tagrisso (osimertinib) to treat late-stage non-small cell lung cancer (NSCLC) (Press release, Genprex, DEC 14, 2022, View Source [SID1234625259]). In 2020, the combination of REQORSA and osimertinib received U.S. Food and Drug Administration’s (FDA) Fast Track Designation for treatment of the Acclaim-1 patient population.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Acclaim-1 is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA Immunogene Therapy, in combination with Tagrisso (osimertinib) in patients with late-stage non-small cell lung cancer (NSCLC) whose disease progressed after treatment with Tagrisso.

The SRC is comprised of three physicians who are principal investigators in the trial. The SRC may recommend that the trial continues at the same dose or at a lower dose, that it escalates to a higher dose, or that the study be terminated altogether due to safety concerns.

"The SRC’s recommendation to increase the dosing of REQORSA is further confirmation of its favorable safety profile and it enables us to advance Acclaim-1 into the final cohort of the Phase 1 dose escalation portion of the study," said Mark Berger, M.D., Chief Medical Officer of Genprex. "We look forward to completing enrollment of this final cohort in the first quarter of 2023."

The Accaim-1 trial includes up to three sequential dose escalation cohorts that will treat study participants with REQORSA intravenously on Day 1 in addition to osimertinib 80 mg fixed dose oral daily tablet during 21-day treatment cycles until disease progression or unacceptable toxicity. The first group received REQORSA IV infusion at 0.06 mg/kg, the second group received 0.09 mg/kg, and the third group will receive 0.12 mg/kg.

Following successful completion of the Phase 1 dose escalation portion of the Acclaim-1 study, the Company will advance into the dose expansion portion of the study, which will evaluate the toxicity profile of REQORSA in combination with Tagrisso in patients with different eligibility criteria, and will also evaluate efficacy and other endpoints.

"The principal advantage of adding the dose expansion portion to Acclaim-1 is to gain efficacy data earlier than we would otherwise have received it from the Phase 2 portion of the study. We also will receive this data in the two distinct patient populations represented by the two expansion cohorts, which we believe will further increase the likelihood of a successful Phase 2 trial," added Dr. Berger.

About Acclaim-1

The Acclaim-1 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA, in combination with Tagrisso in patients with late-stage NSCLC with activating epidermal growth factor receptor ("EGFR") mutations whose disease progressed after treatment with Tagrisso. Genprex expects the dose escalation Phase 1 portion of the Acclaim-1 trial to enroll up to 18 patients to determine the maximum tolerated dose of the combination. The dose expansion Phase 1 portion of the study will then enroll 66 patients, half of whom will be patients who had received only prior Tagrisso treatment and the other half patients who had received prior Tagrisso treatment and chemotherapy, to determine toxicity profiles of patients with different eligibility criteria, as well as efficacy and other endpoints. There will be an interim analysis following the treatment of 19 patients in each cohort. The Phase 2 portion of the study is expected to enroll approximately 74 patients to be randomized 1:1 to receive either REQORSA and Tagrisso combination therapy or Tagrisso monotherapy. The primary endpoint of the Phase 2 portion of the trial is progression-free survival, which is defined as time from randomization to progression or death. An interim analysis will be performed at 25 events.

About REQORSA Immunogene Therapy

REQORSA Immunogene Therapy (quaratusugene ozeplasmid) for non-small cell lung cancer (NSCLC) uses Genprex’s unique, proprietary ONCOPREX Nanoparticle Delivery System, which is the first systemic gene therapy delivery platform used for cancer in human clinical trials. The plasmid portion of REQORSA contains the TUSC2 gene, a tumor suppressor gene. REQORSA consists of the TUSC2 gene containing plasmid encapsulated in a nanoparticle made from lipid molecules with a net positive electrical charge. REQORSA is injected intravenously and is preferentially taken up by cancer cells. Once REQORSA is taken up into a cancer cell, the TUSC2 gene is expressed, and the TUSC2 protein is capable of restoring certain defective functions arising in the cancer cell. 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 programmed cell death, or apoptosis, in cancer cells, and modulates the immune response against cancer cells.

Tagrisso is a registered trademark of AstraZeneca plc and its largest selling drug with 2021 sales of over $5 billion.