On January 8, 2024 Eikon Therapeutics, Inc., a pioneering biotechnology company that leverages advanced engineering to enhance drug discovery and development, reported that the company will provide an overview of clinical and preclinical progress in a presentation at the 42nd Annual J.P. Morgan Healthcare Conference on Monday, January 8th at 9:00 AM Pacific Time (Press release, Eikon Therapeutics, JAN 8, 2024, View Source [SID1234639135]).

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"Eikon has made enormous progress in the development of advanced imaging tools that aid the discovery of important new therapeutics. Our clinical pipeline now includes an immunomodulatory agent, active both by itself and in combination with PD-(L)1 inhibitors, which is entering global Phase 2 studies, as well as a highly selective PARP1 inhibitor for which a Phase 1 program is now enrolling appropriate patients," said Roger M. Perlmutter, M.D., Ph.D., CEO and Board Chair of Eikon Therapeutics. "Beyond these important clinical studies, we have a set of promising development candidates that are expected to advance into the clinic over the next 12 to 24 months. Our progress showcases the integrated clinical development capabilities of Eikon’s team and demonstrates that our proprietary instruments can identify novel chemical matter with especially desirable pharmaceutical properties. These achievements offer the promise of improved treatment outcomes in cancer patients, and in patients afflicted with intractable inflammatory or neurodegenerative conditions."

Key updates:

EIK1001 Advances to Phase 2: Eikon’s most advanced candidate, EIK1001, a systemically administered TLR 7 and 8 co-agonist, has received Investigational New Drug Application (IND) clearance from the U.S. Food and Drug Administration (FDA) and has proceeded into the first of several planned Phase 2 trials focused, in this case, on patients with advanced lung cancer when administered in combination with standard-of-care pembrolizumab plus chemotherapy. The Phase 2 investigation of EIK1001 is supported by compelling data from a Phase 1 trial of over 300 patients, demonstrating its promise both as a standalone agent and in rational combinations with PD-(L)1 inhibitors.
EIK1003 Now Enrolling Patients: Eikon’s selective PARP1 inhibitor, EIK1003, has entered a Phase 1/2 clinical trial at multiple U.S. sites assessing safety and tolerability in adult patients that have received at least one prior PARP inhibitor treatment for specific solid tumors expressing selected deleterious genetic mutations. International sites will join the trial early in 2024. Preclinical studies of EIK1003 (formerly IMP1734) have shown remarkable biochemical and cellular selectivity, positioning it as a potential therapeutic option with less hematologic toxicity when compared to existing PARP1/2 inhibitors. This program is led by Eikon with its collaboration partner, Impact Therapeutics, which is responsible for trial oversight in greater China.
IND-enabling Studies Begin for Brain-Penetrant PARP1 Inhibitor, IMP17307: Collaborating with Impact Therapeutics, Eikon has initiated IND-enabling studies for a brain-penetrant PARP1 candidate and is planning for a Phase 1 clinical trial in 2025.
Discovery Pipeline Progress: Using its proprietary platform, Eikon is conducting lead optimization for several programs including those targeting the androgen receptor and its clinically relevant variants, as well as several targeting key proteins in the DNA damage repair pathway including Werner (WRN). The company anticipates nominating a new clinical candidate in early 2024.
Eikon Systems Business Unit Established: Eikon has developed a suite of instruments that permits detailed, automated characterization of protein motion in living cells. Since most proteins function by interacting with other cellular structures (including other proteins), analysis of the dynamic behavior of individual protein molecules yields information regarding the function and regulation of biologic systems. These tools are increasingly sought after by academic investigators through Eikon’s Technology Access Program. The company expects that instruments from Eikon Systems will help to catalyze the use of protein motion measurements routinely as a means of elucidating biological processes.
An archived recording of Eikon’s presentation at the J.P. Morgan Healthcare Conference can be accessed at: www.EikonTx.com/#news.

On January 8, 2024 Johnson & Johnson (NYSE: JNJ) reported that it has entered into a definitive agreement to acquire Ambrx Biopharma, Inc., or Ambrx (NASDAQ: AMAM), a clinical-stage biopharmaceutical company with a proprietary synthetic biology technology platform to design and develop next-generation antibody drug conjugates (ADCs), in an all-cash merger transaction for a total equity value of approximately $2.0 billion, or $1.9 billion net of estimated cash acquired (Press release, Johnson & Johnson, JAN 8, 2024, View Source [SID1234639134]).

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Ambrx is advancing a focused portfolio of clinical and preclinical programs designed to optimize efficacy and safety of its candidate therapeutics in multiple cancer indications, including ARX517, its proprietary ADC targeting PSMA for metastatic castration-resistant prostate cancer (mCRPC); ARX788, its proprietary ADC targeting human epidermal growth factor receptor 2 (HER2) for metastatic HER2+ breast cancer; and ARX305, its proprietary ADC targeting CD-70 for renal cell carcinoma.

"Ambrx’s ADC technology offers unique advantages in the conjugation of stable antibodies and cytotoxic linker payloads, which results in engineered ADCs that effectively kill cancer cells and limit toxicities," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson Innovative Medicine. "The results seen to date with ARX517 in mCRPC are promising and represent a potential first- and best-in-class targeted therapy for the treatment of this aggressive disease. In addition, Ambrx’s pipeline and ADC platform present exciting future opportunities to deliver enhanced, precision biologics as we look to transform the treatment of cancer and improve patients’ lives."

The planned acquisition presents a distinct opportunity for Johnson & Johnson to design, develop and commercialize targeted oncology therapeutics. Ambrx’s proprietary ADC technology incorporates the advantages of highly specific targeting monoclonal antibodies securely linked to a potent chemotherapeutic payload to achieve targeted and efficient elimination of cancer cells without the prevalent side-effects typically associated with chemotherapy. Building on a legacy of innovation in oncology and in prostate cancer, J&J scientists intend to work with Ambrx researchers, accelerating the Phase 1/2 APEX-01 study (NCT04662580) of ARX517 in advanced prostate cancer, while progressing a pipeline of novel ADC product candidates.

"With a median overall survival of less than two years and novel hormonal therapies moving earlier in the disease, significant unmet need remains in the treatment of mCRPC," said Margaret Yu, M.D., Prostate Cancer Disease Area Leader, Johnson & Johnson Innovative Medicine. "We see a unique opportunity to harness the potential of this innovative ADC platform, and with our deep understanding of prostate cancer, deliver a targeted PSMA therapeutic for addressing the growing needs of the more than 185,000 patients living with metastatic castration-resistant disease today1."

Ambrx was spun out of The Scripps Research Institute in 2003. The company pioneered the expanded genetic code technology platform for incorporation of synthetic amino acid (SAA) into proteins at any selected site using industry standard cell lines. SAAs allow engineered precision biologics with site-specific, homogenous and stable conjugation, overcoming limitations of traditional conjugation technologies.

About the Merger Agreement

Under the terms of the transaction, which was approved by the Johnson & Johnson Board of Directors, Johnson & Johnson (the Company) will acquire all of the outstanding shares of Ambrx’s common stock for $28.00 per share in cash through a merger of Ambrx with a subsidiary of the Company. The closing of the transaction is expected to occur in the first half of 2024, subject to receipt of Ambrx shareholder approval, as well as clearance under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions. The approximately $1.9 billion estimated net value of the transaction is based on Ambrx’s estimated fully diluted shares outstanding, less estimated net cash at the time of closing. Following completion of the transaction, Ambrx’s common stock will no longer be listed for trading on the NASDAQ Global Select Market.

The accounting treatment as a business combination or asset acquisition will be determined on or before the expected close of the transaction.

On January 8, 2024 Simcha Therapeutics ("Simcha"), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, reported that it has entered into a license and option agreement with Janssen Biotech, Inc. ("Janssen"), a Johnson & Johnson company, where Janssen will work to armor select CAR T-based cell therapy candidates with Simcha’s novel proprietary decoy-resistant IL-18 (DR-18) (Press release, Simcha Therapeutics, JAN 8, 2024, View Source [SID1234639133]). The agreement was facilitated by Johnson & Johnson Innovation.

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Under the terms of the agreement, Janssen will develop, manufacture, and commercialize DR-18 armored cell therapies for a set number of programs. In exchange, Simcha will receive an undisclosed upfront fee, potential option exercise fees and development and commercialization milestone payments.

"Interest in developing IL-18 therapeutic approaches for cancer has continued to increase in recent years, tying back to findings published by our scientific founder that reinvigorated therapeutic interest in this cytokine. Armoring CAR T cells to secrete IL-18 is one of the most exciting areas of research, and we are proud to move the research forward with Janssen," said Sanuj Ravindran, M.D., chief executive officer of Simcha. "We will continue to expand our focus on IL-18 and the range of modalities that have potential to significantly improve outcomes for cancer patients, including through our internal development programs and additional strategic partnerships in the future."

On January 8, 2024 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported substantial updates to the promising development of ivonescimab, as well as near-term corporate catalysts that it will present at the 42nd Annual J.P. Morgan Healthcare Conference on Tuesday, January 09, 2024, at 1:30 PM PT in San Francisco, CA (Press release, Summit, JAN 8, 2024, View Source [SID1234639132]).

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AK112-201 (NCT04736823) is an open-label Phase II study evaluating ivonescimab plus chemotherapy across three cohorts of patients. In part, data generated from this trial has supported Summit’s decision to advance ivonescimab into two global Phase III clinical trials. Updated data includes patients from Cohorts 1 & 2 of this study:

Cohort 1: Patients with first line advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (i.e., patients’ tumors do not have actionable mutations in endothelial growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)).
The updated data centers on the 63 patients whose tumors are of squamous histology.
Cohort 2: Patients with second or third line advanced or metastatic NSCLC whose tumors are positive for EGFR mutations (EGFRm) and have progressed following an EGFR tyrosine kinase inhibitor (TKI) (n=19).
Notably, the estimated 1-year overall survival rate was 85.6%, and the 2-year overall survival rate was 64.8% for patients in Cohort 1 with squamous histology NSCLC. After a median follow-up time of 21.0 months, the median overall survival (OS) was not reached.1 The frequency of treatment-related adverse events (TRAEs) leading to discontinuation of ivonescimab was 11%; there were no TRAEs leading to the death of a patient. The most frequent treatment-emergent adverse events were anemia, decreased neutrophil counts, and decreased white-blood cell counts.

The 19 patients in Cohort 2, primarily second or third line patients with EGFRm NSCLC, demonstrated a median overall survival of 22.5 months. After a median follow-up time of 25.8 months, the estimated 1-year overall survival rate was 74%.1 Ivonescimab had an acceptable safety profile in combination with platinum-doublet chemotherapy for patients with advanced or metastatic NSCLC who had progressed following an EGFR-TKI. There were no TRAEs leading to permanent discontinuation of therapy or patient death.

AK112-201 Phase II Trial1

Cohort 1: 1L SQ-NSCLC only
(n=63)

Cohort 2: 2L / 3L+ EGFR-TKI
Progressors NSCLC (n=19)

Overall Response Rate (ORR)*

67%

68%

Disease Control Rate (DCR)*

95%

95%

Median Duration of Response (DOR)*

12.8 months

8.7 months

Median PFS
(95% CI)

11.1 months
(9.5 – 16.3 months)

8.5 months
(5.5 – 13.3 months)

Median OS
(95% CI)

Not Reached
(22.5 months – NE**)

22.5 months
(10.4 months – NE**)

12-month OS Rate

85.6%

73.7%

24-month OS Rate

64.8%

40.9%

* Confirmed responses for patients with at least one post-baseline scan; SQ-NSCLC n=60; EGFR-TKI n=19

** NE – Not Established

AK112-201 is a clinical trial that is sponsored and conducted in China by our collaboration and licensing partner, Akeso, Inc. (HKEX Code: 9926.HK). The aforementioned data related to AK112-201 was generated and analyzed by Akeso.

Summit is enrolling patients in two global Phase III clinical trials involving ivonescimab:

HARMONi intends to evaluate ivonescimab combined with chemotherapy compared to a placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR TKI (NCT05184712), and
HARMONi-3 is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with 1L metastatic squamous NSCLC (NCT05899608).
Near-Term Catalyst Events for Summit & the Development of Ivonescimab

In addition to the ongoing Phase III clinical trials sponsored by Summit, Akeso is sponsoring four Phase III clinical trials investigating ivonescimab in China in NSCLC. Near-term catalyst events for both Summit and Akeso include expected key milestones for two of Akeso’s Phase III randomized clinical trials evaluating ivonescimab in China:

AK112-301, which reflects the patient population of Summit’s HARMONi trial, was submitted for marketing approval to the Chinese health authority in 2023, and a decision from the Chinese Center for Drug Evaluation (CDE) is expected in Q2 2024, along with a read-out of topline data from the study by Akeso, and
AK112-303, which is evaluating monotherapy ivonescimab vs. pembrolizumab in 1L NSCLC patients whose tumors have a PD-L1 TPS >1%, has a planned interim analysis by Akeso, which is expected to be completed in Q2 2024.
Both studies represent ivonescimab in randomized, pivotal clinical trials against the standard of care in their respective settings.

"As the data continues to mature in Phase II studies evaluating ivonescimab, including data related to the survival of patients impacted by these terrible diseases, our belief and conviction in ivonescimab is reinforced," stated Summit’s Chief Executive Officers, Robert W. Duggan and Dr. Maky Zanganeh. "The speed and purpose with which Team Summit acts reflect the opportunity to accomplish our mission of making a significant difference in the lives of patients facing difficult odds from a cancer diagnosis. We believe that the potential created by the differentiated mechanism of action and supporting trial data for ivonescimab deserves a swift development plan to bring ivonescimab to those patients who can benefit most. We are honored to work with our partners at Akeso to continue to strive to achieve this common goal."

In addition to live attendance at the JPM 2024 conference, the audio presentation will be available live from our website: www.smmttx.com.

Update Regarding Current Financial Position

As of December 31, 2023, the company’s preliminary unaudited balance of cash, cash equivalents, and short-term investments was no less than $186 million. This amount is preliminary and is subject to completion of financial closing procedures. As a result, this amount may differ materially from the amount that will be reflected in the Company’s consolidated financial statements for the year ended December 31, 2023.

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18 fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4 times increased binding affinity to VEGF in the presence of PD-1 in vitro.2 This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Summit has begun its clinical development of ivonescimab in NSCLC, commencing enrollment in 2023 in its two Phase III clinical trials. Over 1,600 patients have been treated with ivonescimab in clinical studies in China and Australia, with enrollment beginning in 2023 in Summit’s license territories.

About Lung Cancer

Lung cancer is believed to impact approximately 600,000 people across the United States, United Kingdom, Spain, France, Italy, Germany, and Japan.3 NSCLC is the most prevalent type of lung cancer and represents approximately 80% to 85% of all incidences.4 Among patients with non-squamous NSCLC, approximately 15% have EGFR-sensitizing mutations in the United States and Europe.5 Patients with squamous histology represent approximately 25% to 30% of NSCLC patients.

On January 8, 2024 Incyte (Nasdaq:INCY) reported that it will highlight growth opportunities and provide key updates across its investigational pipeline and commercial portfolio during a presentation today at 7:30 a.m. PT at the 42nd Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Incyte, JAN 8, 2024, View Source [SID1234639131]).

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"As we enter 2024, we see great promise in our portfolio and its potential to drive long-term growth fueled by our strong R&D engine and broad commercial footprint across Oncology and Inflammation & Autoimmunity," said Hervé Hoppenot, Chief Executive Officer, Incyte. "Today, we provide further clarity into several potential high-impact product launches anticipated by 2030. This includes both indication expansion opportunities and the advancement of novel medicines that could broaden our ability to positively affect patients’ lives."

Notably, Incyte announces that the primary endpoint was met in its randomized, placebo-controlled, Phase 2 study evaluating the safety and efficacy of ruxolitinib cream (Opzelura) in adults with mild/moderate hidradenitis suppurative (HS). At Week 16, patients receiving ruxolitinib cream 1.5% twice daily (BID) had significantly greater decreases from baseline versus placebo in total abscess and inflammatory nodule (AN) count, the primary endpoint of the study. The overall safety profile of ruxolitinib cream is consistent with previous data, and no new safety signals were observed. The Phase 2 data will be submitted for presentation at an upcoming scientific meeting in 2024. A Phase 3 study is currently being evaluated.

Additionally, the Company will highlight progress across its Oncology pipeline and the research it is advancing in areas of high potential, including promising early clinical efficacy data for INCB123667, a potent and selective inhibitor of CDK2, demonstrating its potential use as monotherapy or combination therapy for late-stage cancers. In a Phase 1 study of INCB123667, early clinical activity was observed with several patients with amplified/overexpression of CCNE1, a cell cycle regulator and potential predictive biomarker, achieving partial response (PR). Tumor shrinkage was observed across multiple tumor types, including CCNE+ patients with ovarian cancer. The safety profile of for INCB123667 aligns with the mechanism of action.

In addition, Incyte will provide key updates on:

Expanding leadership in myeloproliferative neoplasms (MPNs) and graft-versus-host disease (GVHD) with a pipeline including axatilimab, mCALR and V617F that has disease-modifying potential for patients with graft-versus-host disease and the more than 200,000 patients with myelofibrosis, polycythemia vera and essential thrombocythemia.
Its emerging dermatology franchise, and the intent to maximize the potential of ruxolitinib cream (Opzelura) and expand povorcitinib into multiple indications with high unmet need.
The Company intends to provide additional financial guidance and updates on key clinical programs during its 2023 fourth quarter and year-end earnings conference call.

The J.P. Morgan Healthcare Conference presentation and Q&A session can be accessed at investor.incyte.com. A replay will be archived on the Company’s website for 30 days following the presentation.