On January 17, 2024 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported new interim data for its ongoing THIO-101 Phase 2 trial in non-small cell lung cancer (NSCLC) and outlined key clinical milestones for 2024 (Press release, MAIA Biotechnology, JAN 17, 2024, View Source [SID1234639300]).

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In the latest available data from THIO-101 (November 13, 2023), 60 patients had been dosed with THIO in sequential combination with Libtayo. The patients received either 60mg, 180mg, or 360mg of THIO per dose, and 42 had at least one post baseline assessment completed. The observed disease control was well sustained compared to previous scans.

"We are entering 2024 with strong momentum and great excitement about our programs and pipeline," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "To date, preliminary Phase 2 data on THIO in NSCLC has demonstrated unprecedented rates of disease control and response — measures that vastly outperform the standard of care."

"In addition to NSCLC, our pipeline of immuno-oncology therapies includes THIO orphan drug designations for multiple hard-to-treat cancers, and our research includes THIO-like second-generation telomere-targeting agents. The main objective for the second-generation program is to discover new compounds with potentially improved specificity towards cancer cells relative to normal cells and with potentially increased anticancer activity," Dr. Vitoc continued.

"Multiple milestones are on target for 2024 as enrollment continues in THIO-101, including long-term efficacy as a major clinical inflection point."

Key 2023 Achievements

Positive Preliminary Efficacy Data: Key findings from THIO-101 included:

100% preliminary disease control rate (DCR) in second-line and 88% in third-line, in highly difficult-to-treat patients who already progressed through previous lines of treatment.
DCR across all dose levels met pre-determined statistical requirements earlier than expected to proceed to next stage of the trial.
Third orphan drug designation (ODD) granted to THIO: MAIA’s portfolio of immuno-oncology therapies with ODDs now includes a third hard-to-treat cancer, glioblastoma, the most aggressive and most common type of brain cancer with only limited treatment options.

U.S. FDA Investigational New Drug (IND) Clearance: The FDA cleared U.S.-based evaluation for THIO as part of THIO-101. The trial drew a strong pace of enrollment in 2023 compared with previous NSCLC trials by other drug developers.

Dose Selection: A 180mg/cycle dose of THIO was selected for THIO-101 based on stronger efficacy compared to other doses. The selected dose showed unprecedented disease control and overall response rates for a NSCLC clinical trial.

Next Generation Telomere Targeting Agents: MAIA’s second-generation telomere-targeting program is engaged in research and development for new prodrugs derived from lipid-modified THIO molecules. Capable of acting through similar mechanisms of activity as THIO, the higher potency of these compounds at lower dose levels will be investigated further in 2024.

THIO is the only direct telomere targeting agent currently undergoing clinical development in the field of cancer drug discovery and treatment.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

About THIO-101, a Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of THIO administered prior to cemiplimab (Libtayo) will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. Treatment with cemiplimab (Libtayo) followed by THIO has been generally well-tolerated to date in a heavily pre-treated population. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

On January 17, 2024 Certis Oncology Solutions (Certis), a precision oncology and translational science company focused on combining AI-directed drug development with advanced functional testing, reported that it raised $10 million in a Series C funding round, bringing total raised to $42 million (Press release, Certis Oncology Solutions, JAN 17, 2024, View Source [SID1234639299]). The company also named John R. Tozzi Chairman of its Board of Directors.

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"We welcome John’s leadership and this additional investment at this critical inflection point for our company," said Peter Elman, President and CEO of Certis. "Now serving more than 120 oncology therapeutics companies, we have established the necessary business traction to see a clear path to profitable growth. At the same time, ongoing validation studies give us great confidence that our proprietary CertisAI predictive oncology platform soon will be able to deliver truly personalized cancer treatment at scale."

New Certis Board of Directors Chairman, John Tozzi, who also serves as the Certis Chairman of the Executive and Finance Committees, led the company’s last two internal funding rounds, as well as this most recent raise in which 94% of the company’s top 50 investors participated. "Our investors are passionate about the company’s patient-focused mission and 100% behind its three-pronged strategy for creating shareholder value: building a best-in-class bank of advanced tumor models for cancer research, developing disruptive AI-based intellectual property, and generating services revenue from very specialized contract research to help fund R&D," he said. In 1982 Mr. Tozzi founded Cambridge Investments LLC, an investment management firm, and continues to serve as its CEO and CIO.

On January 17, 2024 Medivir AB (Nasdaq Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported further improved clinical benefit with fostrox + Lenvima as data from the ongoing phase 1b/2a study in advanced hepatocellular carcinoma (HCC) will be presented at the ASCO (Free ASCO Whitepaper) (American Society of Clinical Oncology) GI (Gastrointestinal Cancers) Symposium in San Francisco on January 19 (Press release, Medivir, JAN 17, 2024, View Source;lenvima-shows-further-improved-response-rates-and-time-to-progression-in-advanced-liver-cancer-hcc-at-asco-gi-symposium-302036736.html [SID1234639298]). The updated data further supports accelerating the fostrox development program to initiate a registrational phase 2b study in second-line HCC in 2024.

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– "We are excited by these results in a poor prognosis patient population where low disease control and response rates are usually seen. The updated data presented at ASCO (Free ASCO Whitepaper) GI has further strengthened our belief in the combination of fostrox + Lenvima as a potential treatment for patients with advanced HCC. In addition to the promising clinical benefit, the combination continues to be tolerable with a good safety profile enabling patients to stay on treatment long-term. It reinforces our confidence in advancing fostrox development and engaging with regulatory authorities to discuss final study design of the planned, registrational phase 2b study with accelerated approval intent," says Dr. Pia Baumann, CMO at Medivir.

The data is from a phase 1b/2a open-label, multi-center, dose-escalation and dose-expansion study evaluating the safety and efficacy with fostroxacitabine bralpamide (fostrox) in combination with Lenvima in patients for whom current first- or second-line treatment has proven ineffective or is not tolerable. The combination remains tolerable with no new, unexpected safety events. Only 5% have discontinued fostrox due to adverse events and lower need for dose reductions than expected. With a high and durable disease control rate of 61% at 18 weeks, the majority of patients in this study have continuous clinical benefit.

– "Hepatocellular cancer is a particularly complex disease," says Dr Maria Reig, Director of the Barcelona Clinic Liver Cancer (BCLC) and the Liver Oncology Unit at the Hospital Clinic of Barcelona in Spain, and investigator in the fostrox + Lenvima study. "A clear unmet need remains for safe and effective combination treatments. These data show that fostrox + Lenvima have encouraging results related to clinical outcome in patients with second-line advanced HCC without jeopardizing safety. I look forward to further explore the efficacy of fostrox added to Lenvima in a randomized, controlled trial."

The results from the phase 1b/2a study will be presented by Dr Maria Reig, poster number 476P, at ASCO (Free ASCO Whitepaper) GI on Friday January 19. Medivir will host a conference call to provide additional details from the study, comments on the data and the plans moving forward with fostrox, at 14.00 CET on January 23.

Conference call for investors, analysts and the media
Presenters from Medivir: Jens Lindberg, CEO, Pia Baumann, CMO and Fredrik Öberg, CSO.
Time: Tuesday January 23, 2024, at 14.00 CET

To access the webcast and information about the teleconference, please click HERE

On January 17, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported that the findings of the Phase 1b portion of the Phase 1b/2 study for the second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC) disclosed by Cardiff Oncology in August 2023 have been published in the peer-reviewed journal Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Cardiff Oncology, JAN 17, 2024, View Source [SID1234639297]).

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The publication underscores the safety profile of onvansertib when combined with the standard-of-care (SoC) chemotherapy+bevacizumab. The results show that the combination has a lasting response, indicating its tolerability and efficacy in treating mCRC patients whose tumors harbor various KRAS mutations.

Onvansertib is a highly specific Polo-like kinase 1 (PLK1) inhibitor that has shown tolerability as a single agent and in combination with multiple chemotherapies in various solid tumors. Additional data from the full Phase 1b/2 study for the second-line treatment of patients with KRAS-mutated mCRC will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2024. These compelling insights, along with the agreement from the US FDA, led to Cardiff Oncology’s decision to initiate a first-line trial (CRDF-004) in RAS-mutated mCRC.

"Our groundbreaking Phase 1b study targeted the KRAS-mutated mCRC patient population that has limited effective treatment options, and for whom there has been no new targeted therapy approved in decades. The Phase 1b study revealed the safety and enhanced efficacy of integrating onvansertib, an oral PLK1 inhibitor, with SoC FOLFIRI+bevacizumab in KRAS-mutated second-line mCRC patients," said Dr. Fairooz Kabbinavar MD, FACP, Chief Medical Officer of Cardiff Oncology and one of the article’s lead authors. "Our study showed an improved objective response rate and median progression-free survival compared to historical controls. Encouragingly, the FOLFIRI+bevacizumab+onvansertib combination demonstrated efficacy across multiple KRAS mutations. Our upcoming presentation at AACR (Free AACR Whitepaper) will showcase the full Phase 1b/2 data from all 68 patients in the study. The data from this Phase 1b/2 study serves as the foundation for our CRDF-004 first-line study in RAS-mutated mCRC, which is now open for enrollment at multiple centers."

On January 17, 2024 Partner Therapeutics, Inc. (PTx) reported the publication of a comprehensive review by Mora et al. in the International Journal of Cancer which summarizes the efficacy and safety of anti-GD2 monoclonal antibodies (mAbs) (dinutuximab, dinutuximab beta, and naxitamab) in children with high-risk neuroblastoma when given in combination with Leukine (sargramostim; glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]), recombinant human granulocyte colony-stimulating factor (G-CSF) or no cytokine (Press release, Partner Therapeutics, JAN 17, 2024, View Source [SID1234639296]).

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The review provides a succinct summary of the mechanistic rationale and clinical data supporting the use of Leukine in combination with anti-GD2 mAbs. It also describes why the authors believe it is suboptimal to replace with Leukine with G-CSF in this regimen for mechanistic reasons.

Leukine has been studied extensively in combination with dinutuximab and naxitamab leading to improved patient outcomes. As a result, all clinical trials supporting the FDA-approval of dinutuximab and naxitamab included Leukine and both products are labeled for use in combination with GM-CSF.

"The pleiotropic effects of Leukine contribute to its important role as an immunomodulatory adjuvant in combination with anti-GD2 mAbs," noted Jaume Mora, M.D., Ph.D., Scientific Director of Oncology and Hematology at Sant Joan de Déu Barcelona Children’s Hospital and lead author of the publication. "GM-CSF stimulates neutrophils and macrophages leading to increased cellular phagocytosis and increased ADCC. Further, GM-CSF increases major histocompatibility complex (MHC) class II expression which enhances tumor antigen presentation on dendritic cells that can mediate T cell antitumor effects. For all of these mechanistic reasons, Leukine is a critical component of anti-GD2 therapy." The figure below from the publication depicts these mechanisms.

ABOUT LEUKINE
LEUKINE (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast. The product is commercially available in the United States and accessible through a named patient program operated by Tanner Pharma Group outside of the United States.

LEUKINE is indicated:

To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML).
For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients.
For the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation in adult and pediatric patients 2 years of age and older.
For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older.
For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older.
To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]).
Important Safety Information for Leukine (sargramostim)

Contraindications

Do not administer LEUKINE to patients with a history of serious allergic reaction, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factor, sargramostim, yeast-derived products, or any other component of LEUKINE.

Warnings and Precautions

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If a serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy, and institute medical management. Discontinue LEUKINE permanently for patients with serious allergic reactions.
LEUKINE can cause infusion-related reactions that may be characterized by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease; dose adjustment or discontinuation may be needed.
LEUKINE should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.
Edema, capillary leak syndrome, and pleural or pericardial effusions have been reported in patients after LEUKINE administration. LEUKINE should be used with caution in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure. Such patients should be monitored.
Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease.
If absolute neutrophil count (ANC) > 20,000 cells/mm3 or if white blood cell (WBC) counts > 50,000/mm3, LEUKINE administration should be interrupted, or the dose reduced by half. Monitor complete blood counts (CBC) with differential twice per week.
Discontinue LEUKINE therapy if tumor progression, particularly in myeloid malignancies, is detected during LEUKINE treatment.
Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration needed.
Avoid administration of solutions containing benzyl alcohol (including LEUKINE for injection reconstituted with Bacteriostatic Water for Injection, USP [0.9 % benzyl alcohol]) to neonates and low birth weight infants.

Drug Interactions

Avoid the concomitant use of LEUKINE and products that induce myeloproliferation. Monitor for clinical and laboratory signs of excess myeloproliferative effects.
Adverse Reactions
Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported at a higher frequency than in placebo patients are:

In recipients of autologous bone marrow transplantation (BMT)–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
In recipients of allogeneic BMT–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin
In patients with AML–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema