On August 8, 2024 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported business highlights and financial results for the second quarter that ended June 30, 2024 (Press release, Monte Rosa Therapeutics, AUG 8, 2024, View Source [SID1234645615]).

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"The IND clearance of our VAV1-directed MGD MRT-6160 represents a major corporate milestone for Monte Rosa, signifying what we believe to be the first clinical-stage, rationally designed MGD for a non-oncology indication," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "Our MRT-2359 program for MYC-driven solid tumors is in an ongoing Phase 1/2 study and we look forward to announcing the recommended Phase 2 dose, sharing updated clinical efficacy and safety results from the dose escalation arm of the trial, and initiating enrollment of our Phase 2 expansion cohorts in the second half of the year. Our second immunology/inflammation program, MRT-8102, a NEK7-directed MGD targeting diseases driven by IL-1β and the NLRP3 inflammasome, continues to advance and we expect to submit an IND application in the first half of next year. Our strategic collaboration with Roche has been progressing rapidly, and we are very pleased to announce today that we have reached our first set of research milestones, which we believe further validates the productivity of our QuEEN Discovery Engine. Our strong balance sheet, augmented by our recent financing, is expected to provide cash runway into H1 2027, funding the Company through multiple anticipated milestones including proof-of-concept readouts for our three lead programs."

RECENT HIGHLIGHTS

MRT-2359, GSPT1-directed MGD for MYC-driven solid tumors

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Monte Rosa continues to evaluate MRT-2359 in a Phase 1/2 clinical trial in MYC-driven solid tumors (NCT05546268). In June 2024, the Company announced that it had obtained encouraging initial safety and pharmacodynamic data from the 0.5 mg dose using the 21 days on, 7 days off regimen. This regimen represents dosing of MRT-2359 twice as frequently per cycle compared to the 5 days on, 9 days off regimen previously evaluated in this study. Based on the favorable safety assessment for the 0.5 mg dose, the Company continues to evaluate a higher 0.75 mg, 21 days on, 7 days off dose cohort. In the second half of the year, Monte Rosa expects to make a final determination of the MRT-2359 recommended Phase 2 dose, share updated clinical activity and safety results from the dose escalation arm of the trial, and initiate enrollment of MRT-2359 Phase 2 expansion cohorts.
MRT-6160, VAV1-directed MGD for systemic and neurological autoimmune/inflammatory diseases

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Monte Rosa reported that its Investigational New Drug (IND) submission for MRT-6160 has been accepted by the U.S. Food and Drug Administration (FDA). Initiation of a Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study is expected this summer and initial clinical results are anticipated in Q1 2025.
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In July, Monte Rosa reported the publication of a review article titled, VAV1 as a putative therapeutic target in autoimmune and chronic inflammatory diseases, co-authored by Prof. Dr. Markus F. Neurath, Friedrich-Alexander-University Erlangen-Nürnberg, and Prof. Leslie J. Berg, University of Colorado School of Medicine, in the peer-reviewed journal Trends in Immunology, a Cell Press journal. The publication highlights how novel approaches targeting VAV1 have therapeutic potential in T and B-cell-mediated autoimmune and chronic inflammatory diseases.
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In June, Monte Rosa presented preclinical data at the EULAR 2024 conference demonstrating that MRT-6160 inhibited disease progression, pro-inflammatory cytokines, and autoantibody production in the collagen-induced arthritis murine model of rheumatoid arthritis.
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In May, Monte Rosa presented preclinical data at Digestive Disease Week 2024 demonstrating that MRT-6160 inhibited colitis disease progression and colon inflammation, lowered inflammatory mucosal cytokines, and reduced expression of IBD-associated genes in a T-cell transfer murine model of colitis.
MRT-8102, NEK7-directed MGD for inflammatory diseases driven by IL-1β and the NLRP3 inflammasome

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In March, Monte Rosa announced the initiation of IND-enabling studies for MRT-8102, a first-in-class NEK7-directed MGD for the treatment of inflammatory diseases driven by interleukin-1β (IL-1β) and the NLRP3 inflammasome, critical elements of the inflammatory process. MRT-8102 has demonstrated highly favorable central nervous system (CNS) exposure and degradation in a study in non-human primates, supporting its potential development in neurologic indications and obesity, in addition to potential use in gout, pericarditis, and other peripheral inflammatory conditions. The Company is evaluating applications across multiple inflammatory disorders.
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Monte Rosa expects to submit an IND application for MRT-8102 in H1 2025.
CDK2 and Cyclin E1-directed MGD programs

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In May, Monte Rosa announced a new discovery program for CCNE1 (Cyclin E1)-directed MGDs for the treatment of CCNE1-amplified tumors. CCNE1, a key component of the cell cycle and a known driver of many cancers, is generally considered an undruggable target by conventional modalities.
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Monte Rosa is progressing both programs to development candidate nominations and expects to nominate a development candidate for the CDK2-directed MGD program by year end.
Additional Corporate Updates

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Monte Rosa announced today that it achieved pre-specified research milestones and earned milestone payments under its strategic collaboration and licensing agreement with Roche. In October 2023, Monte Rosa entered into a strategic collaboration and licensing agreement with Roche to discover and develop MGDs against targets in cancer and neurological diseases. Under the terms of the agreement, Monte Rosa received an upfront payment of $50 million and is eligible to receive future preclinical, clinical, commercial, and sales milestone payments that could exceed $2 billion, as well as tiered royalties.

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In May, the Company announced an underwritten public offering providing gross proceeds of approximately $100 million.
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In May, Monte Rosa announced three leadership team promotions: Sharon Townson, Ph.D., to Chief Scientific Officer; Phil Nickson, Ph.D., J.D., to Chief Business and Legal Officer; and Jennifer Champoux to Chief Operating Officer.
ANTICIPATED MILESTONES

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Announce the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study and report Phase 1 clinical activity and safety results in H2 2024. The Company also plans to initiate the Phase 2 portion of the study before year-end. The Company is evaluating Phase 2 expansion cohorts in high-prevalence c-MYC-driven tumors, including hormone receptor-positive breast cancer and prostate cancer, as well as tumor types and patient populations driven by L- and N-MYC including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and solid tumors with amplifications of L- and N-MYC.
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Initiate a Phase 1 SAD/MAD study with MRT-6160 in healthy volunteers in mid-2024; report results from the Phase 1 study in Q1 2025. Monte Rosa expects to subsequently initiate proof-of-concept (POC) studies in autoimmune/inflammatory diseases, including ulcerative colitis and rheumatoid arthritis, with additional potential POC studies in dermatology, rheumatology, and neurology indications.
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Submit an IND application for MRT-8102 in H1 2025.
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Nominate a development candidate for the CDK2 preclinical program in 2024.

SECOND QUARTER 2024 FINANCIAL RESULTS

Collaboration Revenue: Collaboration revenue for the second quarter of 2024 was $4.7 million, compared with $0 during the same period in 2023. Collaboration revenue represents revenue recorded under the Roche License and Collaboration agreement.

Research and Development (R&D) Expenses: R&D expenses for the second quarter of 2024 were $28.1 million, compared to $29.1 million during the same period in 2023. R&D expenses were driven by the successful achievement of key milestones in our R&D organization, including the continuation of the MRT-2359 clinical study, the progression and growth of our preclinical pipeline, the preparation of MRT-6160 to enter the clinic, and the continued development of the Company’s QuEEN discovery engine. Non-cash stock-based compensation constituted $2.6 million of R&D expenses for Q2 2024, compared to $2.3 million in the same period in 2023.

General and Administrative (G&A) Expenses: G&A expenses for the second quarter of 2024 were $9.3 million compared to $8.1 million during the same period in 2023. The increase in G&A expenses resulted from increased headcount, stock-based compensation expense, and fees paid to consultants to support growth and operations. G&A expenses included non-cash stock-based compensation of $1.9 million for the second quarter of 2024, compared to $1.9 million for the same period in 2023.

Net Loss: Net loss for the second quarter of 2024 was $30.3 million, compared to $32.0 million for the first quarter of 2024.

Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of June 30, 2024, were $267.1 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $197.8 million as of March 31, 2024.

The Company expects its cash and cash equivalents to be sufficient to fund planned operations and capital expenditures into the first half of 2027.

About MRT-2359

MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About MRT-6160

MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in preclinical studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple systemic and neurological autoimmune indications, such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and dermatological disorders. Preclinical studies have demonstrated that MRT-6160 can inhibit disease progression in several in vivo autoimmunity models.

About MRT-8102

MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NLRP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including gout, cardiovascular disease, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. In a non-human primate model, MRT-8102 was shown to potently, selectively, and durably degrade NEK7, and resulted in near-complete reductions of IL-1β models following ex vivo stimulation of whole blood. MRT-8102 has shown a favorable profile in non-GLP toxicology studies.

On August 8, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the discontinuation of the Phase 3 KeyVibe-008 trial based on the recommendation of an independent Data Monitoring Committee (DMC) (Press release, Merck & Co, AUG 8, 2024, View Source [SID1234645614]). The trial is evaluating the investigational fixed-dose combination (coformulation) of vibostolimab, an anti-TIGIT antibody, and pembrolizumab (KEYTRUDA), Merck’s anti-PD-1 therapy, in combination with chemotherapy compared to atezolizumab in combination with chemotherapy, for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). At a pre-planned analysis, data showed that the primary endpoint of overall survival (OS) met the pre-specified futility criteria. Additionally, when compared to patients in the control arm, patients in the vibostolimab and pembrolizumab fixed-dose combination arm experienced a higher rate of adverse events (AEs) and immune-related AEs. A comprehensive analysis of this study is ongoing.

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Merck is notifying study investigators of the decision and that patients should stop ongoing treatment with the fixed-dose combination of vibostolimab and pembrolizumab and be offered the option to be treated with atezolizumab. Results will be shared with the scientific community.

"Small cell lung cancer remains a difficult disease to treat, as evident by the seven percent five-year survival rate and limited advancements in treatment options," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "Innovative research plays a critical role in improving our understanding to help patients achieve better outcomes, and while we hoped the results would be different, we remain committed to investigating novel approaches to treat this debilitating disease. We are extremely grateful to all of the patients, caregivers and investigators for their participation in this study."

Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations.

In SCLC, Merck and Daiichi Sankyo recently announced that the first patient has been dosed in the IDeate-Lung02 Phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) in patients with relapsed SCLC versus treatment of physician’s choice of chemotherapy. Merck and Daiichi Sankyo also expanded their existing global co-development and co-commercialization agreement for three investigational DXd antibody-drug conjugates to include Merck’s MK-6070, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager that is currently being evaluated in a Phase 1/2 clinical trial (NCT04471727). The companies are planning to evaluate MK-6070 in combination with I-DXd in certain patients with SCLC, as well as other potential combinations. Merck obtained MK-6070 through its acquisition of Harpoon Therapeutics.

Ongoing Phase 3 studies evaluating the vibostolimab and pembrolizumab fixed-dose combination in lung cancer, which are routinely monitored by external data monitoring committees, include KeyVibe-003, KeyVibe-006 and KeyVibe-007. Interim external data monitoring committee safety reviews have not resulted in any study modifications to date and the studies are undergoing ongoing comprehensive safety monitoring.

About KeyVibe-008

KeyVibe-008 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT05224141) evaluating a fixed-dose combination of vibostolimab and pembrolizumab (MK-7684A) in combination with etoposide and platinum chemotherapy followed by the vibostolimab and pembrolizumab fixed-dose combination versus atezolizumab in combination with etoposide and platinum chemotherapy followed by atezolizumab for the first-line treatment of patients with ES-SCLC. The primary endpoint is OS, and key secondary endpoints include progression-free survival, objective response rate, duration of response, all as assessed by blinded independent central review (BICR). The trial enrolled 460 patients who were randomized (1:1) to receive:

Vibostolimab/pembrolizumab fixed-dose combination (pembrolizumab 200 mg and vibostolimab 200 mg intravenously [IV] every three weeks [Q3W] for four cycles) in combination with etoposide and platinum chemotherapy (carboplatin or cisplatin) Q3W for a total of approximately 12 weeks followed by additional cycles of the vibostolimab/pembrolizumab fixed-dose combination until any of the conditions for discontinuation are met; or
Atezolizumab (1,200 mg Q3W) in combination with etoposide and platinum chemotherapy (carboplatin or cisplatin) Q3W for a total of approximately 12 weeks followed by additional cycles of atezolizumab until any of the conditions for discontinuation are met.
About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.48 million new cases and 1.8 million deaths from lung cancer globally. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. The two main types of lung cancer are non-small cell and small cell. Small cell lung cancer accounts for about 15% of all lung cancers. Patients with small cell lung cancer have a particularly poor prognosis, with an estimated five-year survival rate of 7% for patients in the United States with any stage of the disease. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.

On August 8, 2024 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported its second quarter 2024 financial and operating results (Press release, Lineage Cell Therapeutics, AUG 8, 2024, View Source [SID1234645613]). The Company will host a conference call today at 4:30 p.m. Eastern Time to discuss these results and to provide a business update.

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"The second quarter was highlighted by clinical and preclinical execution alongside expanded awareness and data updates on our lead program," stated Brian M. Culley, Lineage CEO. "As the cell transplant field expands and continues to deliver exciting clinical outcomes, we are excited about our validating partnership and the collective expertise of the team at Roche and Genentech, as well as their ongoing leadership of the OpRegen program through presentations at scientific conferences and internal thought leader events, including Roche’s Virtual Ophthalmology Day, hosted just last month. We continue to support the ongoing Phase 2a clinical study and also have initiated activities under the recently established services agreement with Genentech, enabling our partners to take advantage of our cell transplant expertise to more fully investigate the potential of the OpRegen program. In parallel, we are focused on activities in support of returning our second cell transplant program, OPC1, into the clinic this year for the treatment of spinal cord injury, a condition with growing awareness of its unmet need and commercial opportunity."

"Importantly, our continued inclusion within the Russell 3000 Index, can help our efforts to broaden investor awareness of, and support for, Lineage as a uniquely positioned cell transplant company, one with a pharma-validated lead program and a platform technology of internally-owned clinical and preclinical assets, which is focused on growing our internally-owned cGMP capabilities in support of process and intellectual property development," added Mr. Culley.

Recent Operational Highlights

RG6501 (OpRegen)
Continued execution under our collaboration with Roche and Genentech, a member of the Roche Group, across multiple functional areas, including support for the ongoing Phase 2a clinical study in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Initiated activities under recently established services agreement with Genentech to support ongoing development of OpRegen. Lineage is providing additional clinical, technical, training and manufacturing services, fully funded by Genentech, that further support the ongoing advancement and optimization of the OpRegen program and include: (i) activities to support the ongoing Phase 1/2a study and currently-enrolling Phase 2a study; and (ii) additional technical training and materials related to Lineage’s cell therapy technology platform to support commercial manufacturing strategies.
Positive clinical data from long-term follow-up of patients from the Phase 1/2a clinical study of OpRegen presented by David Telander, MD, PhD, Retinal Consultants Medical Group, at the 2024 Retinal Cell & Gene Therapy Innovation Summit.
Mean best corrected visual acuity (BCVA) gain of 5.5 letters at 24 months (n=10) in Cohort 4 patients (less advanced GA)
Mean BCVA gains greater among patients with improvement in outer retinal structure (n=5, +7.4 letters)
Maintenance or increases in external limiting membrane (ELM) and retinal pigment epithelium (RPE) layer area at 24 months observed in patients with extensive coverage of OpRegen across the areas of GA (n=5)
Data suggest OpRegen may counteract RPE cell dysfunction and cell loss in patients with GA by providing support to remaining retinal cells, with multi-year effects observed following a single administration
Preclinical results from a surgical development study of OpRegen presented by Rachel N. Andrews, DVM, PhD, DACVP, Genentech, a member of the Roche Group, at 2024 Association for Research in Vision and Ophthalmology Annual Meeting (2024 ARVO).
OPC1
DOSED (Delivery of Oligodendrocyte Progenitor Cells for Spinal Cord Injury: Evaluation of a Novel Device) clinical study for the treatment of subacute and chronic spinal cord patient start-up activities continue.
Hosted the 2nd Annual Spinal Cord Injury Investor Symposium, in partnership with the Christopher & Dana Reeve Foundation.
Balance Sheet Highlights

Cash, cash equivalents, and marketable securities of $38.5 million as of June 30, 2024 is expected to support planned operations into Q4 2025.

Second Quarter Operating Results

Revenues: Lineage’s revenue is generated primarily from collaboration revenues and royalties. Total revenues for the three months ended June 30, 2024 were $1.4 million, a net decrease of $1.8 million as compared to approximately $3.2 million for the same period in 2023. The decrease was primarily driven by less collaboration and licensing revenue recognized from deferred revenues under the collaboration and license agreement with Roche.

Operating Expenses: Operating expenses are comprised of research and development (R&D) expenses and general and administrative (G&A) expenses. Total operating expenses for the three months ended June 30, 2024 were $7.3 million, a decrease of $0.9 million as compared to $8.2 million for the same period in 2023.

R&D Expenses: R&D expenses for the three months ended June 30, 2024 were $2.9 million, a net decrease of $1.0 million as compared to $3.9 million for the same period in 2023. The net decrease was primarily driven by $0.6 million for our OPC1 program and $0.3 million for our preclinical programs.

G&A Expenses: G&A expenses for the three months ended June 30, 2024 were approximately $4.3 million, a net increase of approximately $0.1 million as compared to $4.2 million for the same period in 2023. The increase was primarily driven by stock-based compensation expense and personnel costs.

Loss from Operations: Loss from operations for the three months ended June 30, 2024 were $5.9 million, an increase of $0.9 million as compared to $5.0 million for the same period in 2023.

Other Income/(Expenses): Other income (expenses) for the three months ended June 30, 2024 reflected other income of $0.1 million, compared to other expenses of ($0.2) million for the same period in 2023. The change was primarily driven by exchange rate fluctuations related to Lineage’s international subsidiaries, fair market value changes in marketable equity securities, and interest income earned within our money market accounts.

Net Loss Attributable to Lineage: The net loss attributable to Lineage for the three months ended June 30, 2024 was $5.8 million, or $0.03 per share (basic and diluted), compared to a net loss attributable to Lineage of $5.2 million, or $0.03 per share (basic and diluted), for the same period in 2023.

Conference Call and Webcast

Interested parties may access the conference call on August 8th, 2024, by dialing (800) 715-9871 from the U.S. and Canada and should request the "Lineage Cell Therapeutics Call." A live webcast of the conference call will be available online in the Investors section of Lineage’s website. A replay of the webcast will be available on Lineage’s website for 30 days and a telephone replay will be available through August 15th, 2024, by dialing (800) 770-2030 from the U.S. and Canada and entering conference ID number 6024260.

On August 8, 2024 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence ("AI") company developing targeted and transformative cancer therapies using its proprietary RADR AI and machine learning ("ML") platform with multiple clinical-stage drug programs, reported operational highlights and financial results for the second quarter 2024, ending June 30, 2024 (Press release, Lantern Pharma, AUG 8, 2024, View Source [SID1234645612]).

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"The team at Lantern Pharma is making solid, thoughtful and disciplined progress in our clinical trials and in our collaborative research and AI efforts. This past quarter saw a significant milestone where our clinical trials are getting to the point of having initial patient data that we can share, including our unique Harmonic clinical trial for never smokers with lung cancer. We continue to also improve the functionality and abilities of our AI platform, RADR, to guide the next phase of our therapeutic programs which will be heavily marked by trials with combination regimens, and ADC development." said Panna Sharma, President and CEO of Lantern Pharma.

Highlights of AI-Powered Pipeline:

Ø LP-300: The Harmonic Phase 2 Clinical Trial – Preliminary results at the completion of the 7-patient lead-in part of the Harmonic study demonstrated predictable safety profiles that are consistent with the chemotherapy regimen alone and seemed to demonstrate clinical benefit for 6 out of the 7 patients – an 86% clinical benefit rate (CBR). No patients experienced dose limiting toxicities, and no discontinuations were observed due to treatment related toxicity. Six patients experienced clinical benefit from the combination of LP-300 and chemotherapy while 1 patient experienced progressive disease. The clinical benefit rate is 86% for this group with an objective response rate (ORR) of 43%. Of the 6 patients experiencing clinical benefit – 3 patients showed partial responses with an average tumor size reduction of 51% and 3 patients have stable disease with an average tumor size reduction of 13%. Encouraging preliminary efficacy results were observed regardless of prior tyrosine kinase inhibitor (TKI) treatment(s), demographics, and metastatic disease sites. In the initial set of patients, those having low to intermediate TMB (tumor mutation burden) were found to be responsive to LP-300 + chemotherapy.

The phase 2 Harmonic clinical trial sites in the US, and certain sites in Japan are screening for eligible patients and we expect the pace of enrollment to increase in the coming months. This past quarter we also initiated IRB approvals and site initiation visits in Asia. The expansion of the Phase 2 clinical trial in Japan and Taiwan is expected to accelerate the collection of patient and response data that are needed for the next-stage of development of LP-300, a therapeutic for the treatment of relapsed and inoperable primary adenocarcinoma of the lung given in combination with chemotherapy. Additionally, it may also bring a needed therapeutic option for never-smokers with NSCLC in Japan and Taiwan, where one-third or more of all lung cancer diagnoses are made among those who have never smoked. Dr. Yashushi Goto, a physician and researcher focused on lung cancer at the National Cancer Center of Japan, will be leading the phase 2 trial in Japan, where the incidence of non-small cell lung cancer (NSCLC) in never-smokers is double or more than that of the United States. Lantern believes that this improves the positioning for drug-candidate LP-300 to develop collaborative and co-development partnerships with global biopharma companies with a primary focus in serving the Asian markets.

The Harmonic trial is assessing the effect of LP-300 in combination with standard-of-care chemotherapy in never-smoker patients with relapsed NSCLC where they have failed TKI therapies. Globally, never-smokers with NSCLC are a growing population of patients and do not respond well to PD-1/PD-L1-based therapies or the available chemotherapy doublets, leaving them with reduced treatment options. In the US it is estimated that the treatment indication of never smokers with NSCLC has an annual market potential of $1.5 billion, and a global estimated annual market potential of over $2.6 billion.

Ø LP-184 – Seven cohorts of patients have been enrolled and dosed – in escalating doses – in the ongoing Phase 1A clinical trial – a first-in-human Phase 1 basket trial across multiple solid tumor indications that are advanced and refractory to existing standard-of-care therapies. We expect to reach a dosage level in the coming cohort where therapeutic concentrations of the drug should be attainable based on our pharmacokinetic and pharmacodynamic analyses. The trial is actively enrolling patients across multiple US centers that have relapsed/refractory advanced solid tumors, such as pancreatic cancer, glioblastoma (GBM), lung, triple-negative breast cancer, and multiple other solid tumor types with DNA damage response deficiencies. No dose-limiting toxicities have been observed to date in the LP-184 trial, and the Company believes that enrollment should be complete this year and on-track for an initial readout of safety and molecular correlation data by the close of the year. The dosage and safety data obtained in the Phase 1A trial are expected to be used to advance the central nervous system (CNS) indications for a future Phase 1b/2 trial to be sponsored by Lantern’s wholly owned subsidiary, Starlight Therapeutics, as well as other later phase trials in select tumors that have shown superior responsiveness to LP-184 and meet with genomically guided criteria related to drug-response. Lantern has also made advancements toward a key milestone related to the development of a quantitative PCR-based molecular diagnostic test that may help in identifying patients with the best likelihood of response and benefit from treatment with LP-184.

AI and preclinical studies are also ongoing to further refine drug combination studies supporting the use of LP-184 to improve the durability or overall response rates in combination with FDA approved drugs that are widely used in cancer treatment – especially PARP inhibitors, and immune checkpoint inhibitors. Globally, the aggregate annual market potential of LP-184’s target indications is estimated to be approximately $12+ billion, consisting of $4.5+ billion for CNS cancers and $7.5+ billion for solid tumors.

Ø LP-284 – The third cohort of patients are being dosed, and no dose-limiting toxicities have been observed in the LP-284 Phase 1A clinical trial. We expect to open additional sites in the US throughout the third quarter with the potential to advance to Phase 1B and 2 by the close of 2024 or early 2025. LP-284 has shown nanomolar potency across multiple published in vitro and in vivo studies, including mantle cell lymphoma (MCL), double hit lymphoma (DHL), and other advanced NHL cancer subtypes with DNA damage response deficiencies, notably those with compromised functioning of the ataxia-telangiectasia mutated (ATM) gene due to mutations or deletions. Nearly all MCL, DHL, and HGBL patients relapse from the current standard-of-care agents and there is an urgent and unmet need for novel improved therapeutic options for these patients. In the US and Europe, MCL, DHL, and HGBLs are diagnosed in 16,000-20,000 patients each year and have an estimated annual market potential of over $3+ billion.

We have also begun a review of some notable mechanisms-of-action of LP-284 that may be leveraged in other diseases and conditions. Lantern expects to review those preclinical studies and findings later this quarter.

RADR Platform Growth and Development:

Ø RADR continues to advance in size, scope, and capabilities and is also progressing towards becoming recognized as a standard for AI-driven drug development in oncology – for both early-stage development and later-stage patient biomarker and combination therapy identification. Lantern will potentially focus additional data growth efforts of the RADR platform on: drug sensitivity data, combination treatment outcome data, and biomarker data in rare cancers, and on emerging synthetic lethal targets that are aimed at accelerating the development of new therapies for Lantern and its partners. The scope of RADR’s data has broadened with a strategic focus on additional classes of compounds, detailed data on chemical and biochemical features and drug-interaction data. Real-world data from clinical studies such as those being obtained from liquid biopsy, and data from preclinical combination studies that aim to define drug interaction and optimal dosage are being incorporated into the datapoints and data sets powering RADR.

Lantern also leveraged the RADR platform in developing a drug-development collaboration with Oregon Therapeutics with a focus on accelerating the development and decision path towards a first-in-human launch of the drug-candidate, XCE853 into the clinic. The AI-enabled collaboration with Oregon Therapeutics aims to refine and expand the positioning of XCE853, a novel protein disulfide isomerase (PDI) inhibitor, in new and targeted oncology indications, including for drug-resistant tumors. Lantern Pharma is receiving equal IP co-ownership and drug development rights in newly discovered biomarkers, novel indications, and use for new pharmacological strategies for XCE853.

Additionally, the RADR platform’s generative AI capabilities, focusing on molecular optimization and automated feature extraction to improve understanding and prediction of molecular dynamics, safety, and drug-drug interactions are planned to increase in functionality and scope in the coming quarters for both small molecule development and increasingly for ADC development, analytics and characterization.

Second Quarter 2024 Financial Highlights

Ø Balance Sheet: Cash, cash equivalents, and marketable securities were approximately $33.3 million as of June 30, 2024, compared to approximately $41.3 million as of December 31, 2023. The quarterly cash burn rate continues to reflect our capital-efficient, collaborator-centered business model.

Ø R&D Expenses: Research and development expenses were approximately $3.9 million for the quarter ended June 30, 2024, compared to approximately $3.6 million for the quarter ended June 30, 2023.

Ø G&A Expenses: General and administrative expenses were approximately $1.5 million for the quarter ended June 30, 2024, compared to approximately $1.6 million for the quarter ended June 30, 2023.

Ø Net Loss: Net loss was approximately $4.96 million (or $0.46 per share) for the quarter ended June 30, 2024, compared to a net loss of approximately $4.75 million (or $0.44 per share) for the quarter ended June 30, 2023.

Ø Total Share and Warrant Count: There were no warrant exercises during the three months ended June 30, 2024. Following June 30, 2024, additional warrants were exercised which increased the Company’s total shares outstanding and reduced the number of outstanding warrants. As of the date of this press release, the Company has 10,764,725 shares of common stock outstanding, and outstanding warrants to purchase 70,000 shares of common stock.

Additional Operational Highlights:

Ø A publication was made in the AACR (Free AACR Whitepaper) Journals, Cancer Research Communications showcasing the potential for LP-184 to synergize with PARP inhibitors in a wide range of solid tumors that are HRD (homologous repair deficient). The preclinical findings in the paper illustrate the potential of LP-184 to be a pan-HRD cancer therapeutic – which could be the first drug of this type in this class. We believe the data and results support clinical evaluation of LP-184 in a large subset of HRD solid tumors.

Ø New data and scientific findings conducted in conjunction with Drs. Yong Du and Shiaw-Yih (Phoebus) Lin at MD Anderson were presented at The Immuno-Oncology Summit 2024. The findings showcased what Lantern believes to be the role of LP-184 to be combined with checkpoint inhibitors to provide greater response in TNBC due to synergy and to potentially transform TNBC tumors that are unresponsive (cold) to checkpoint inhibitors to responsive (hot). The poster was titled: LP-184, a Novel Acylfulvene, Sensitizes Immuno-Refractory Triple Negative Breast Cancers (TNBCs) To Anti-PD1 Therapy by Affecting the Tumor Microenvironment.

Ø With a focus on increasing visibility and awareness of the Lantern portfolio and capabilities, the Company launched Webinar Wednesdays in April. They are currently planned to be held on the last Wednesday of each month and are designed to showcase industry leaders in AI and drug development, as well as clinicians working in collaboration with Lantern’s portfolio of drug-candidates. The next three Webinar Wednesdays will include the topics of: 1) LP-300’s clinical results to-date, 2) RADR and our industry-leading ability to predict if a molecule or drug-compound will cross the BBB (Blood-Brain-Barrier), and 3) The role of LP-184 in synergizing with checkpoint inhibitors and IO agents.

Earnings Call and Webinar Details:

Lantern will host its 2nd quarter 2024 earnings call and webinar today, August 8th, 2024, at 4:30 p.m. ET. A link to register can be accessed at: Lantern 2nd Quarter 2024 Earnings Call & Webinar Link

Ø Related presentation materials will be accessible at: View Source
Ø A replay of the 2nd quarter 2024 earnings call and webinar will be available at: View Source

On August 8, 2024 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported second quarter 2024 financial results and provided a corporate update (Press release, Kura Oncology, AUG 8, 2024, View Source [SID1234645611]).

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"This past quarter was highlighted by strong execution across the organization," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "We completed enrollment in our KOMET-001 registration-directed trial of ziftomenib in patients with relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML), and we were delighted to have ziftomenib receive Breakthrough Therapy Designation from the FDA in that indication. In the KOMET-007 study, the safety, tolerability and clinical activity of ziftomenib continue to support advancement of ziftomenib into the frontline (1L) population, and the Phase 1b expansion study in combination with venetoclax and azacitidine (ven/aza) and cytarabine plus daunorubicin (7+3) is now open for enrollment. We are generating a robust clinical data package to support the broad development of ziftomenib, including enrollment of more than 100 patients in the KOMET-007 study, and we look forward to providing an update on this study at a medical meeting later this year, followed by topline data from our registration-directed trial in early 2025."

Recent Highlights

Completion of enrollment in pivotal trial of ziftomenib in R/R NPM1-mutant AML – In May 2024, Kura completed enrollment of 85 patients in the Phase 2 portion of KOMET-001, a registration-directed clinical trial of its menin inhibitor, ziftomenib, in patients with R/R NPM1-mutant AML. NPM1-mutant AML accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists. The Company expects to report topline data from the trial in early 2025.
Breakthrough Therapy Designation for ziftomenib in NPM1-mutant AML – In April 2024, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to ziftomenib for the treatment of R/R NPM1-mutant AML. FDA granted BTD based on data from the KOMET-001 trial of ziftomenib in patients with R/R NPM1-mutant AML. BTD is awarded for a drug that treats a serious or life-threatening condition and may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies.
Phase 1b expansion portion of KOMET-007 open for enrollment – Kura recently began dosing patients in the Phase 1b expansion portion of its KOMET-007 combination study of ziftomenib. The Phase 1b expansion study includes multiple combination cohorts, including ven/aza in newly diagnosed NPM1-mutant or KMT2A-rearranged AML and 7+3 in newly diagnosed NPM1-mutant or KMT2A-rearranged AML without qualification for high-risk disease. Each combination cohort is expected to enroll approximately 20 patients at 600 mg. The Company expects to present updated data from the KOMET-007 study at a medical meeting in the fourth quarter of 2024.
IND for ziftomenib in GIST; proof-of-concept study to begin in early 2025 – Earlier today, Kura announced FDA clearance of its IND application for ziftomenib for the treatment of advanced gastrointestinal stromal tumors (GIST) in combination with imatinib. Preclinical data suggest ziftomenib has potential to resensitize patients to imatinib and induce deep, durable responses. The Company expects to present the preclinical data for the combination at an upcoming scientific meeting, followed by a proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025.
Preclinical data support potential for menin inhibitor in diabetes – In June 2024, Kura reported data showing that ziftomenib induces insulin production, improves insulin sensitivity and reduces insulin resistance in a preclinical in vivo model of type 2 diabetes. Ziftomenib demonstrated meaningful levels of glycemic control, including reduced fasting blood glucose levels and %HbA1C within 27 days, as well as consistent improvement in both insulin sensitivity and insulin production. The data were presented at the American Diabetes Association (ADA) Scientific Sessions in Orlando. The Company expects to nominate the first in a series of next-generation development candidates targeting diabetes in early 2025.
First patient dosed in study of KO-2806 and adagrasib in KRASG12C-mutated NSCLC – Kura recently began dosing patients in its study of KO-2806, a next-generation farnesyl transferase inhibitor (FTI), in combination with adagrasib in KRASG12C-mutated non-small cell lung cancer (NSCLC). The Company’s findings suggest that combining KO-2806 with adagrasib may drive tumor regressions and enhance both duration and depth of antitumor response in preclinical models of KRASG12C-mutated NSCLC. The study of KO-2806 and adagrasib is supported by a clinical collaboration and supply agreement with Mirati, now a Bristol Myers Squibb company.
Financial Results

Research and development expenses for the second quarter of 2024 were $39.7 million, compared to $28.2 million for the second quarter of 2023.
General and administrative expenses for the second quarter of 2024 were $16.7 million, compared to $11.8 million for the second quarter of 2023.
Net loss for the second quarter of 2024 was $50.8 million, compared to a net loss of $37.2 million for the second quarter of 2023. This included non-cash share-based compensation expense of $8.4 million, compared to $7.0 million for the same period in 2023.
As of June 30, 2024, Kura had cash, cash equivalents and short-term investments of $491.5 million, compared to $424.0 million as of December 31, 2023.
Based on its operating plan, management expects that cash, cash equivalents and short-term investments will fund current operations into 2027.
Forecasted Milestones

Present updated data from the KOMET-007 trial of ziftomenib in combination with ven/aza and 7+3 at a medical meeting in the fourth quarter of 2024.
Report topline data from the KOMET-001 registration-directed trial of ziftomenib in NPM1-mutant R/R AML in early 2025.
Present preclinical data supporting opportunity for ziftomenib in GIST at a scientific meeting in the second half of 2024.
Initiate proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025.
Nominate a next generation menin inhibitor development candidate in early 2025.
Identify the maximum tolerated dose for KO-2806 as a monotherapy in the second half of 2024.
Complete enrollment of two expansion cohorts in KURRENT-HN and identify the optimal biologically active dose of tipifarnib and alpelisib by the end of 2024.
Present data from the KURRENT-HN trial of tipifarnib in combination with alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) in the first half of 2025.
Conference Call and Webcast

Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, August 8, 2024, to discuss the financial results for the second quarter 2024 and to provide a corporate update. The live call may be accessed by dialing (877) 300-8521 for domestic callers and (412) 317-6026 for international callers and entering the conference ID: 10190278. A live webcast and archive of the call will be available online from the investor relations section of the company website at www.kuraoncology.com.