On February 13, 2023 Panbela Therapeutics, Inc. (Nasdaq: PBLA), ("Panbela"), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported that, primarily as a result of the January 30, 2023 closing of its public offering of approximately $15 million of common stock and warrants, Panbela has regained compliance with applicable listing standards of The Nasdaq Stock Market ("Nasdaq") (Press release, Panbela Therapeutics, FEB 13, 2023, View Source [SID1234627106]).

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Panbela Regains Nasdaq Compliance

Nasdaq has issued notice that Panbela has regained compliance for continued listing of its common stock. On February 9, 2023, Panbela received a letter from Nasdaq confirming that Panbela has cured the previously identified minimum bid price and stockholders’ equity deficiencies under Nasdaq Listing Rules 5550(a)(2) and 5550(b)(1), respectively, and that Panbela is in compliance with all applicable listing standards. Panbela’s previously scheduled delisting determination appeal hearing has been canceled, and its common stock will continue to be listed and traded on Nasdaq.

Panbela Closes $15 million Public Offering

On January 30, 2023, Panbela closed its previously announced public offering consisting of (i) 6,675,000 shares of its common stock (or pre-funded warrants in lieu thereof) and (ii) warrants to purchase up to 13,350,000 shares of its common stock (the "Public Warrants") at a purchase price of $2.25 per share and associated Public Warrants (or $2.249 per pre-funded warrant and associated Public Warrants). All of the pre-funded warrants have been exercised. The Public Warrants have a cash exercise price of $2.75 per share of common stock, were exercisable upon issuance, and will expire five years following the date of issuance. The Public Warrants also contain cashless exercise provisions, subject to certain conditions.

Roth Capital Partners acted as lead placement agent and Maxim Group LLC acted as coplacement agent of the offering.

Gross proceeds from the offering, before deducting placement agent fees and offering expenses, were approximately $15.0 million. Panbela intends to use the net proceeds from the offering for the continued clinical development of its product candidates ivospemin (SBP-101) and eflornithine (CPP-1X), working capital, business development and other general corporate purposes, which may include repayment of debt.

The securities described above were offered pursuant to a registration statement on Form S-1 (File No. 333-268854), as amended, that was declared effective by the U.S. Securities and Exchange Commission ("SEC"), on January 25, 2023, and a registration statement on Form S-1 (File No. 333-269421) filed pursuant to Rule 462(b) with the SEC on January 26, 2023. The offering was made solely by means of a prospectus. Copies of the prospectus relating to and describing the terms of the offering may be obtained at the SEC’s website at www.sec.gov or by contacting Roth Capital Partners, LLC, 888 San Clemente Drive, Suite 400, Newport Beach, CA 92660 or by email at [email protected].

About Panbela’s 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.

Ivospemin (SBP-101)

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 February 13, 2023 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported preliminary safety and anti-tumor activity data from the dose expansion phase of the Company’s ongoing Phase 1 clinical trial of lorigerlimab, a bispecific, tetravalent PD-1 × CTLA-4 DART molecule (Press release, MacroGenics, FEB 13, 2023, View Source [SID1234627105]). This investigational molecule was designed to block PD-1 with enhanced CTLA-4 blockade on dual PD-1/CTLA-4-expressing cells, such as tumor-infiltrating lymphocytes (TILs), while maintaining maximal PD-1 blockade on all PD-1-expressing cells. The preliminary data is being presented in a poster titled "Lorigerlimab, a Bispecific PD-1 × CTLA-4 DART Molecule in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase 1 Expansion Cohort" (Poster #155) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO-GU) Cancers Symposium taking place February 16-18, 2023, in San Francisco, CA.

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Cohort Expansion Results Update

The ASCO (Free ASCO Whitepaper)-GU abstract included data as of September 10, 2022; updated data as of a December 12, 2022 cut-off are included below and will be presented at ASCO (Free ASCO Whitepaper)-GU.

As of the December 12, 2022 data cut-off, 118 patients with mCRPC, melanoma, non-small cell lung cancer or microsatellite-stable colorectal cancer were enrolled in the cohort expansion phase of the lorigerlimab Phase 1 study at the dose of 6.0 mg/kg, administered intravenously every three weeks (Q3W). Confirmed objective responses were observed across the histology-specific cohorts; preliminary efficacy results for mCRPC are presented in the poster and below.

Preliminary Safety Results

The safety analysis is based on 127 patients who received lorigerlimab at a dose of 6 mg/kg Q3W, including 118 enrolled in the four dose expansion cohorts plus nine patients from dose escalation. Median exposure was 14.4 weeks (range: 1.9 – 100.1 weeks) with a median of four infusions administered per patient. Twenty-four patients remained on lorigerlimab as of the December 12, 2022 data cut-off; 103 discontinued for the following reasons: progressive disease (PD) (n=66), adverse events (AE) (n=31), patient/physician decision (n=5), or death due to PD (n=1).

The results demonstrated a manageable overall safety profile. Treatment-related AEs (TRAEs) occurred in 86.6% of patients, with the most common among them (≥15%) being fatigue, rash, pruritus, hypothyroidism, and pyrexia. Rates of grade ≥3 TRAEs and immune-related AEs were 34.6% and 7.9%, respectively. AEs resulted in treatment discontinuation in 24.4% of patients. There were no fatal AEs related to lorigerlimab.

Preliminary Anti-tumor Activity in mCRPC Cohort

As of the December 12, 2022 data cut-off, 42 patients had been enrolled in the mCRPC expansion cohort. Patients had previously received a median of two prior therapies (range: 1 – 9) for advanced disease, with 35 patients (83.3%) having received docetaxel and 34 patients (81.0%) having received androgen receptor antagonist therapy. The median exposure to lorigerlimab was 19.2 weeks (range: 3.3 – 55.1 weeks), with a median of five infusions administered per patient.

A total of 35 patients with mCRPC had measurable soft tissue disease per RECIST v1.1 at study entry. Nine of the 35 patients (25.7%) achieved confirmed partial responses (cPR). The median duration of response for these nine patients was 4.6 months (range: 2.8 – 8.6+ months), with four patients remaining on lorigerlimab as of data cut-off. Among the other five patients who had achieved cPR, four discontinued due to unrelated adverse events, and one patient discontinued due to physician decision.

Reductions in PSA levels of ≥ 50% were observed in 12 of 42 patients (28.6%), and 9 of the 12 maintained PSA50 response ≥ 3 months. Nine of 42 patients (21.4%), including the nine who achieved cPR, had reductions in their PSA levels of ≥ 90% as of the data cut-off.

"To date, checkpoint inhibition has not fared well in the treatment of patients with late-stage mCRPC. Previously, anti-CTLA-4 therapy, whether alone or in combination with an anti-PD-1 agent, resulted in increased risk for immune-related toxicity with very modest anti-tumor activity," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We designed lorigerlimab to have preferential blockade on dual PD-1/CTLA-4-expressing cells such as TILs, which are most abundant in the tumor microenvironment. As part of this study, biomarker analyses indicated that lorigerlimab was shown to induce T-cell activation as evidenced by an increased frequency of circulating Ki67+ and ICOS+ T cells. We believe we are seeing the benefit of lorigerlimab’s design and are very encouraged by this latest data set from our ongoing Phase 1 study. Looking forward, we plan to initiate a Phase 2 study of lorigerlimab in patients with mCRPC later this year and anticipate providing an update on the proposed study later this quarter."

ASCO-GU Poster Presentation

MacroGenics’ lorigerlimab poster presentation will be available for on-demand viewing on the ASCO (Free ASCO Whitepaper)-GU website and on the "Events & Presentations" page on MacroGenics’ website at View Source

About Lorigerlimab

Lorigerlimab (previously known as MGD019) is an investigational, bispecific IgG4-based, Fc-bearing DART molecule that was designed to enhance blockade on PD-1 and CTLA-4 dual-expressing, tumor-infiltrating lymphocytes, while maintaining maximal PD-1 blockade on all circulating PD-1-expressing cells. In addition to the study described above and presented in the poster, MacroGenics is also evaluating the activity of lorigerlimab in combination with vobramitamab duocarmazine (previously known as MGC018, an investigational B7-H3-directed antibody-drug conjugate) in a study in patients with advanced solid tumors.

On February 13, 2023 IMV Inc. (Nasdaq: IMV; TSX: IMV) ("IMV" or the "Company"), a clinical-stage biopharmaceutical company developing a portfolio of immune-educating therapies based on its novel DPX platform to treat solid and hematologic cancers, reported positive preliminary data from the VITALIZE Phase 2B trial evaluating its lead DPX product, maveropepimut-S ("MVP-S"), in combination with pembrolizumab in patients with relapsed, refractory Diffuse Large B Cell Lymphoma ("r/r DLBCL") (Press release, IMV, FEB 13, 2023, View Source [SID1234627104]).

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Key initial findings from the ongoing VITALIZE trial:

8 Patients with an ECOG1 score of 0-1 have been enrolled in arm 1 of the study. Of these, 6 have so far been evaluable for efficacy;

Of these 6 evaluable patients, 3 patients showed confirmed complete responses, 1 patient was assessed with stable disease as best response and 2 patients were assessed with progressive disease as best response; and

2 patients with poor level of baseline functionality (ECOG ≥ 2) failed to stay on study through to the first scan and therefore could not be evaluated.

Overall Response Rate ("ORR") will be communicated when the totality of stage one data are available for definitive assessment.

"VITALIZE is our most advanced and rigorous trial to date, and we are encouraged by the way the data for MVP-S are trending. This is the most refractory population of patients we have treated so far, and to show complete, confirmed clinical responses is notable. These positive initial results, combined with the accelerating recruitment of the AVALON study in platinum resistant ovarian cancer add, we believe, to the growing industry enthusiasm about the potential for MVP-S in multiple tumor settings," said Andrew Hall, CEO of IMV.

1 ECOG is a measure of patient functionality and is measured according to a standardized measure ranging from 0-5. Oken et al., Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-655. PMID: 7165009

About the VITALIZE Study

The VITALIZE Phase 2B trial is a randomized, parallel group, Simon two-stage study designed to assess IMV’s lead candidate, MVP-S, in combination with pembrolizumab with (arm 1) or without (arm 2) cyclophosphamide. Across the arms of this study, the combination will be evaluated in up to 30 patients in stage one (two arms of 15) with the option to expand to up to a total of 102 subjects in stage two with r/r DLBCL who have received at least two prior lines of systemic therapy and who are ineligible or have failed autologous stem cell transplant (ASCT) or CAR-T therapy.

About the AVALON study

The AVALON study is an open label, company-sponsored phase 2b, single arm trial evaluating the efficacy and safety of MVP-S and intermittent low-dose cyclophosphamide (CPA) in patients with platinum-resistant ovarian cancer. The study is a Simon two-stage design where up to 41 subjects will be evaluated in stage one, with the option to expand to up to a total of 73 patients in stage two. Patients participating in the trial will receive two doses of subcutaneous MVP-S once every three weeks, followed by an MVP-S dose once every eight weeks, plus low-dose oral CPA on a repeating cycle of one week on/one week off.

On February 13, 2023 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapies based on its proprietary arenavirus platform, reported that it has achieved a $10 million non-dilutive milestone payment under its collaboration agreement with Roche to develop HB-700, a novel arenaviral immunotherapy for KRAS-mutated cancers (Press release, Hookipa Pharma, FEB 13, 2023, View Source [SID1234627103]). The success-based milestone payment reflects the start of the HB-700 manufacturing process to support a Phase 1 clinical trial. HOOKIPA plans to submit an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration in the first half of 2024.

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"We’re really pleased to start the year strongly by achieving this milestone in our collaboration with Roche to develop HB-700 for KRAS-mutated cancers," said Joern Aldag, Chief Executive Officer at HOOKIPA. "We’re excited to advance the HB-700 program, our third in oncology, and we’re eager to explore the potential of our technology in addressing another unmet need in cancer."

In October 2022, HOOKIPA and Roche announced a strategic collaboration agreement to license and develop HB-700 for KRAS-mutated cancers and an option for a second, undisclosed arenaviral immunotherapy. Through the collaboration, HOOKIPA is conducting research and early clinical development through Phase 1b for HB-700. Upon the completion of the Phase 1b trial, Roche has the right to assume development responsibility and to commercialize licensed products across multiple indications upon approval. Under the collaboration, HOOKIPA is eligible for research, development and commercialization milestone-based payments up to approximately $930 million for both programs, plus royalties.

About KRAS-mutated cancers
KRAS is a gene that acts as an on/off switch for cell growth. When there is a mutation, or error, in the gene, cells can grow out of control. KRAS mutations are among the most common mutations that cause cancer. While KRAS-mutated, tumor-specific treatments exist, there remains an opportunity to target a broader range of KRAS-mutations simultaneously and thereby potentially help more people impacted by these cancers.

About HOOKIPA’s arenaviral technology
HOOKIPA’s novel, replicating arenaviral technology has demonstrated the ability to induce potent antigen-specific T cell responses and promising anti-tumor activity in a Phase 1 clinical trial which treated patients with advanced Human Papillomavirus 16-positive head and neck cancers. Preclinical studies have also demonstrated the ability of arenaviral immunotherapies to break self-tolerance and induce potent T cell responses to tumor self-antigens and mutated epitopes, or target parts of a mutated, cancer-causing gene. These findings provide scientific rationale for the HB-700 program.

About HB-700
HB-700 is an investigational arenaviral immunotherapy designed to treat KRAS-mutated lung, colorectal, pancreatic and other cancers. HB-700 is a replicating 2-vector therapy that targets the most common KRAS mutations (G12D, G12V, G12R, G12C and G13D) and thereby may benefit more patients than single mutation inhibitors.

On February 13, 2023 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported topline results from its pivotal Phase 3 PRESERVE 1 trial showing that the trial achieved its co-primary endpoints related to severe neutropenia with statistical significance; however, early anti-tumor efficacy data, including overall response rate (ORR) and preliminary measures of survival, favored the placebo arm (Press release, G1 Therapeutics, FEB 13, 2023, View Source [SID1234627102]). Other clinical trials of trilaciclib in combination with different chemotherapies in patients with extensive-stage small cell lung cancer and triple negative breast cancer did not demonstrate this adverse survival signal. Given that placebo outperformed trilaciclib in these analyses of PRESERVE 1, the Company has made the decision to discontinue the colorectal (CRC) trial. The Data Monitoring Committee (DMC) has independently reached the same conclusion.

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PRESERVE 1 was designed to evaluate the efficacy and safety of trilaciclib administered in addition to triplet therapy with FOLFOXIRI + bevacizumab in patients with metastatic CRC. Detailed Phase 3 results will be presented at an upcoming scientific congress and submitted for publication.

PRESERVE 1 achieved its co-primary endpoints showing clinically meaningful and statistically significant reductions in both occurrence of severe neutropenia during induction (placebo=20% vs. trilaciclib=1%; p<0.001) and mean duration of severe neutropenia in Cycles 1 through 4 (placebo=1.3 days vs. trilaciclib=0.1 days; p<0.001). In addition, patients receiving trilaciclib had a clinically meaningful reduction in the rate of chemotherapy-induced diarrhea, including a 50% reduction in the rate of Grade 3/4 diarrhea and a 30% reduction in the rate of any grade diarrhea, compared to placebo. Further, patients receiving trilaciclib experienced fewer chemotherapy dose reductions and delays. Other secondary measures of myeloprotection also favored trilaciclib, including reductions in Febrile Neutropenia (placebo=5% vs. trilaciclib=0%) and ESA administration (placebo=7% vs. trilaciclib=3%).

However, despite the achievement of the co-primary endpoints and other secondary measures of myeloprotection and tolerability, early anti-tumor efficacy data, including overall response rate (ORR), favor patients receiving placebo compared to trilaciclib (61% and 50% ORRs, respectively). Given the differential in these anti-tumor efficacy metrics and the low likelihood of achieving the progression-free survival (PFS) and overall survival (OS) endpoints, G1 has made the decision to discontinue PRESERVE 1.

"PRESERVE 1 is the first clinical evaluation of trilaciclib in a 5-FU-based chemotherapeutic backbone," said Raj Malik, M.D., G1 Therapeutics’ Chief Medical Officer. "This study reaffirms that trilaciclib is a highly effective drug for myeloprotection that all but eliminated neutropenia as a concern for patients with CRC in the trial, which helps inform our ongoing combination studies with other highly myelotoxic regimens like ADCs. Unfortunately, despite the robust myeloprotection and improved tolerability, early survival indicators, including the observed overall response rate in this trial, favor patients receiving placebo. These results in PRESERVE 1 are inconsistent with what we’ve observed in other tumors with different chemotherapy backbones. As a result of these topline results, we have made the decision to terminate this study. While we are disappointed, we are grateful for the patients, clinical investigators and their office staff, our partner Simcere, and the G1 team—all of whom contributed to the conduct of this trial."

"All of us at G1 are disappointed in this surprising outcome for patients with CRC, but we remain committed to the potential of trilaciclib to impact the lives of many cancer patients in other indications," said Jack Bailey, G1 Therapeutics’ Chief Executive Officer. "We are increasingly encouraged by the real-world performance of trilaciclib in patients with extensive stage small cell lung cancer and look forward to upcoming readouts in our other ongoing trials."

About PRESERVE 1

PRESERVE 1 is a global multi-center, randomized placebo-controlled, line extension pivotal Phase 3 trial of trilaciclib in 326 patients with metastatic CRC receiving first line trilaciclib administered to triplet therapy with FOLFOXIRI (fluorouracil (5-FU), folinic acid, oxaliplatin and irinotecan) and bevacizumab. The regimen was given for two consecutive days of every 14-day cycle. Patients received trilaciclib or placebo administered prior to their chemotherapy for a maximum of 12 cycles of induction followed by maintenance therapy.

Webcast and Conference Call

G1 will host a webcast and conference call at 8:30 a.m. ET today to discuss PRESERVE 1 and the Company’s ongoing commercial and clinical programs.

Please note that there is a new process to access the call via telephone. To register and receive a dial in number and unique PIN to access the live conference call, please follow this link to register online. While not required, it is recommended that you join 10 minutes prior to the start of the event. A live and archived webcast will be available on the Events & Presentations page of the company’s website: www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.