On January 8, 2024 Jubilant Therapeutics Inc., a clinical-stage biotechnology company pioneering the development of a first-in-class CoREST (Co-repressor of Repressor Element-1 Silencing Transcription) inhibitor JBI-802 with the dual activity on LSD1 and HDAC6, reported preliminary safety, pharmacokinetic and initial efficacy results of the Phase I trial in advanced cancer patients (Press release, Jubilant Therapeutics, JAN 8, 2024, View Source [SID1234639120]). Furthermore, the study results provide a human proof of principle for expanding the development of JBI-802 in Essential Thrombocythemia (ET) and related Myeloproliferative Neoplasms (MPN/MDS) with thrombocytosis.

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The data from first 11 patients with advanced cancer revealed a dose-proportional increase in exposure across cohorts and a strong correlation between the exposure and the on-target effects of platelet decrease, indicating that pharmacological relevant level of LSD1 inhibition have been achieved. At the same time, platelet decrease is the only adverse event above grade 1 observed in these patients, which differentiates JBI-802 from LSD1-only inhibitors. Specifically, no AEs (Adverse Events) of anemia has been observed, which is potentially due to the positive benefit of inhibition of HDAC6 in erythrocytes. Also, there are no reports of Dysgeusia, an adverse event that has been observed with LSD1-only inhibitors.

Among the 11 patients, two were NSCLC (Non-small Cell Lung Cancer) patients, both had progressed on doublet immunotherapy, nivolumab+ipilimumab as first line treatment and both showed anti-tumor activity. Both the patients were treated at lower dose level (10mg) where no relevant decrease of platelets is seen, suggesting that in patients with sensitive tumors this dose can be pharmacologically active with a desirable safety profile.

Both NSCLC patients had failed first line treatment with doublet immunotherapy, nivoluman/ipilumab prior to enrolling in the JBI-802 study. The first patient had a STK11 mutation, known to decrease the effectiveness of immunotherapy, present in around 10% of NSCLC patients (higher frequency in lung adenocarcinoma). JBI-802 showed a confirmed partial response in this IO-refractory NSCLC patient with a 39% decrease in the target lung tumor mass. The tumor shrinkage outcome was accompanied by a complete resolution of pancoast syndrome (lung lesion affecting the nerves of brachial plexus). The response appears to be durable after nine cycles and the patient remains on JBI-802 therapy.

The second patient had both lung lesion and liver metastasis, which are known to confer resistance to immunotherapy and lead to poor prognosis. Treatment with JBI-802 resulted in over 50% shrinkage of the patient’s liver metastasis and a complete resolution of related portal hypertension, edema and improvement of quality of life.

Dr. Alexander Starodub, The Christ Hospital – Cincinnati, treating physician for the above patients commented, "The anti-tumor activity seen in these two NSCLC patients is remarkable given the poor prognosis based on their genetic and metastatic pattern. The 10 mg dose of JBI-802 was well-tolerated without any clinically significant adverse effects and the initial clinical data suggest a good therapeutic index for JBI-802."

Preclinical studies showed a synergistic anti-tumor effect by combining immunotherapy and JBI-802 in xenograft models. In addition, the CoREST inhibition was reported to sensitize immunotherapy resistant tumors, especially those with STK11 mutations. Taken together, the preliminary efficacy data from the JBI-802 Phase I study suggest the opportunity that a combination between immunotherapy and JBI-802 could bring a new therapy option to such patient populations with limited treatment options.

In addition, the on-target dose/exposure-proportional decrease in platelet constitute a proof-of-principle that JBI-802 can be an active compound in hematological malignancies like Essential Thrombocythemia (ET) and other MPN/ MDS characterized by thrombocytosis. A follow up Phase I/II study in MPN/ET and MPN/MDS with thrombocytosis is being planned in the first quarter of this year to investigate JBI-802 as potential novel treatment option.

On January 8, 2024 Akeso, Inc. (9926.HK) ("Akeso," "we," or the "Company") reported that Michelle Xia, Ph.D, the founder, chairwoman, president, and CEO of Akeso, will deliver a keynote speech focusing on the Company’s achievements in the development of new bispecific antibody drug therapeutics and the Company’s 2024 key milestones at the 42nd Annual J.P. Morgan Healthcare Conference, to be held January 8-11, 2024 in San Francisco, California (Press release, Akeso Biopharma, JAN 8, 2024, View Source;innovative-clinical-development-roadmap-302028539.html [SID1234639119]). The presentation will take place on Tuesday, January 9, at 4:30 PM PST.

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Thanks to clear strategic vision and efficient execution by our leadership and team,we delivered yet another exceptional performance, surpassing expectations and successfully achieving all of our stated goals in 2023. We are seeking to achieve the followings potential milestones that may take place in 2024 and into early 2025:

Approval of four NDAs/sNDAs across five indications
NDAs/sNDAs filing across four indications for three drugs
Topline data readout from up to five registrational trials
Completing enrollment for up to four registrational trials
Initiating up to five new Phase III trials
In addition, Akeso continues to plan for first-in-human clinical trials for a range of products currently in preclinical evaluation, including, for the first time, an antibody-drug conjugate (ADC).

Updated Clinical Data and Milestone Outlook for Ivonescimab (PD-1/VEGF Bispecific)

We currently have three Phase III clinical trials for ivonescimab at varying stages of progress:

AK112-301, for which the NDA has been submitted for approval to the CDE,
AK112-303, for which enrollment has completed
AK112-306, for which we are currently enrolling.
We are presenting updated data from our Phase II clinical trials, supporting our rapid development of ivonescimab across multiple indications.

Updated Data for AK112-201 (NCT04736823)

AK112-201 is an open-label, Phase II study evaluating ivonescimab plus chemotherapy across three cohorts. The patients with tumors of squamous histology in Cohort 1 help support our decision to initiate the AK112-306 Phase III clinical trial comparing ivonescimab against tislelizumab plus chemotherapy; the patients in Cohort 2 supported our earlier decision to enter into AK112-301 comparing ivonescimab plus chemotherapy against chemotherapy alone.

AK112-201 Phase II Trial

Cohort 1: 1L SQ-NSCLC only

(n=63)

Cohort 2: 2L / 3L+ EGFR-TKI

Progressors NSCLC (n=19)

Median Follow-up Time

21.0 months

25.8 months

Overall Response Rate (ORR)*

67 %

68 %

Disease Control Rate (DCR)*

95 %

95 %

Duration of Response

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

For Cohort 1, the frequency of treatment-emergent adverse events (TEAEs) leading to discontinuation of ivonescimab was 11%; there were no treatment-related adverse events (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. In Cohort 2, ivonescimab had an acceptable safety profile. There were no TRAEs leading to permanent discontinuation of therapy or patient death.

Key Near-Term Milestones of Ivonescimab:

For the NDA for ivonescimab based on AK112-301, 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. Ivonescimab is expected to become the world’s first bispecific drug combining immunotherapy and anti-angiogenesis.
Phase III data readout of ivonescimab monotherapy versus pembrolizumab monotherapy as first-line treatment for NSCLC patients with positive PD-L1 expression is expected in Q2 2024.
Based on this data, the Company will submit an NDA for this indication as appropriate.
Phase III enrollment completion of ivonescimab in combination with chemotherapy versus tislelizumab in combination with chemotherapy for first-line treatment of advanced or metastatic squamous NSCLC is expected in the second half of 2024.
Phase III completion by Summit of the global enrollment of ivonescimab (AK112/SMT112) combined with chemotherapy in patients with EGFR-mutated, locally advanced or metastatic nsq-NSCLC who have progressed after treatment with a third-generation EGFR -TKI is expected in the second half of 2024.
Potential initiation of Phase III clinical trials for ivonescimab in additional tumor types in 2024.
Milestone Outlook for Cadonilimab (PD-1/CTLA-4 Bispecific)

Following the Company’s benchmark sales of cadonilimab, the world’s first PD-1/CTLA-4 bispecific antibody, in 2023, the Company is poised to achieve additional important breakthroughs in 2024 that will significantly enhance clinical and commercial value.

In January 2024, the NMPA accepted the sNDA for cadonilimab in combination with chemotherapy as first-line treatment for recurrent or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
NDA submission of cadonilimab + chemotherapy ± bevacizumab for first-line treatment for advanced cervical cancer is expected in Q1 2024.
Phase III enrollment completion of cadonilimab for adjuvant treatment of hepatocellular carcinoma (HCC) is expected in Q4 2024.
Phase III data readouts for first-line GC/GEJ cancer and first-line cervical cancer in 2024.
Potential initiation of Phase III clinical trials for cadonilimab in additional tumor types in 2024.
Other Potential Milestones for Oncology Products

In terms of other significant oncology drug milestones, the Company is expected to reach several important milestones in 2024 to early 2025. Two bispecific antibodies, AK129 (PD-1/LAG3) and AK130 (TIGIT/TGFβ), are anticipated to enter Phase II, while ADC and neurodegenerative diseases candidates will undergo human clinical trials for the first time.

Additionally, the CDE will also make a decision on the NDA for penpulimab for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC). Finally, additional combination therapy data is anticipated to be announced.

Key Near-Term Milestones of Non-Oncology Products

NDA decision expected in 2024 on ebronucimab (PCSK9) for the treatment of hypercholesterolemia and heterozygous familial hypercholesterolemia.
NDA decision expected in 2024 on ebdarokimab (IL-12/IL-23) for the treatment of moderate-to-severe psoriasis.
Phase III enrollment completion of gumokimab (IL-17) for ankylosing spondylitis.
Phase III data readout of gumokimab (IL-17) for Moderate-to-severe psoriasis.
Based on this data, an NDA submission for gumokimab (IL-17) for the treatment of moderate-to-severe psoriasis.
Potential initiation of a Phase III clinical trial for manfidokimab (IL-4R) for the treatment of moderate atopic dermatitis.
Over the next five years, Akeso has high expectations of launching around 10 internally developed blockbuster drugs, both in China and worldwide, thereby achieving successful commercialization. Akeso has established and continuously advances its integrated and efficient system of discovery, development, production, and sales of its innovative drugs and pipeline candidates.

On January 8, 2024 ConcertAI, LLC, a leading oncology real-world evidence data and AI technology company, and NeoGenomics, Inc., a leading oncology testing services company, reported a broad collaboration to advance large-scale hematological research solution to investigate real-world clinical practice and outcomes in hematological malignancies (Press release, NeoGenomics Laboratories, JAN 8, 2024, View Source;generative-ai-solutions-at-ash-2023-302028062.html [SID1234639118]).

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Few diseases are as complex as hematological malignancies. The number of alternative treatments considered for patients at different points throughout their care is more varied and individualized than what is seen in diagnosis and management of solid tumors. Hematological malignancies require surveillance of patients over multiple time periods with numerous clinical and diagnostic measures to assess sustained response to treatment or relapse.

Combining ConcertAI’s longitudinal clinical data with NeoGenomics’ comprehensive biomarkers derived from hundreds of hematological tests, we are able to establish a robust and definitive real-world evidence (RWE) hematology solution. The collaboration advances molecular and genetic data solutions for the entire drug development lifecycle, from early clinical development planning to post-approval epidemiological studies. The scale and volume of the combined dataset, which covers over one million patient lives across over 1,000 oncology clinics, provides coverage of key biomarkers throughout the entire patient treatment journey and across multiple lines of therapy, which enables high-value research and quality of care insights. This is the first population-scale hematology data set, which is both large and broad enough to minimize selection bias, to offer an actionable representation of the hematological prevalent disease in the US. The multi-modal combination of Electronic Medical Record (EMR) and rich biomarker data allows for the latest causal inference methodologies, increasingly preferred by the U.S. FDA and other regulatory bodies, and clinical AI methodologies with assurance of high representativeness and generalizability.

"ConcertAI has spent the last three years with biopharma researchers, medical societies, patient advocacy groups, and academic teams to define requirements for truly definitive, insight-enabling research solutions for hematological malignancies," said Jeff Elton, PhD, CEO of ConcertAI. "We did this with the collective goal of having a decade or more of data, richness, consistency in biomarker coverage and the ability to integrate across clinical data and diagnostic modalities. NeoGenomics captures the majority of all U.S. hematologic malignancy testing being sent out to a reference laboratory. It was obvious to both teams that combining our data and capabilities could solve the legacy challenges of depth, breadth, and limited longitudinality."

With rich cytogenetics, morphology, flow cytometry, FISH, and molecular hematological data, this collaboration now has the potential to apply the latest Generative Artificial Intelligence and other complementary approaches that are historically limited by data set sizes and lack of standardization. Hematological diseases can be stable under treatment for years and then enter a period of non-response and relapse. New AI approaches offer the potential to define predictable patterns linked to specific biomarker patterns, aligned to different treatment approaches, and directly associated with outcomes, which can inform new therapeutic programs, clinical trial designs, and treatment strategies.

"We are excited to see the collaboration produce a rich and meaningful dataset to fuel life science research, clinical trial planning and real-world data application," said Lindsey Gasparini, Vice President of Informatics at NeoGenomics. "Our expansive footprint in hematologic testing will enable an important view into clinical work up, diagnosis, and monitoring through longitudinal and multi-modal testing for the community oncologist. ConcertAI has an impressive collection of research-grade clinical data in oncology and hematology, and the power in linking that with the depth and breadth of NeoGenomics data is transformational," Gasparini continued.

The companies will be launching a hematology-focused collaborative version of ConcertAI’s Clinical Trial Optimization solution later in Q1, supporting study design and optimizing all aspects of trial planning, with multiple clinical development initiatives planned.

On January 8, 2024 Abbisko Therapeutics (HKEX code: 02256) reported that its investigational innovative CSF-1R inhibitor pimicotinib（ABSK021） has been granted orphan drug designation（ODD） by the European Medicines Agency (EMA) for the treatment of inoperable tenosynovial giant cell tumor (TGCT) (Press release, Abbisko Therapeutics, JAN 8, 2024, View Source [SID1234639117]).

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Following the successful ODD granted by the EMA, the product will benefit from incentives, including protocol assistance, fee reductions, procedural advantages for market authorization, and market exclusivity and so on. In addition to the above-mentioned benefits within the European Union, member states may also offer specific stimuli for orphan drugs.

Previously, in June 2023, pimicotinib was granted the Priority Medicines（PRIME） designation by the EMA, which aims to expedite the review process for promising medicines in areas of unmet medical needs.

In early December 2023, Abbisko entered into an agreement with Merck that granted it an exclusive license to commercialize pimicotinib for all indications in the Chinese mainland, Hong Kong, Macau, and Taiwan. Merck also obtained an exclusive option for global commercial rights of pimicotinib, subject to the terms and conditions as agreed between the parties. Pursuant to the terms of the license agreement, Abbisko will receive a one-time, non-refundable down payment of US$ 70 million. In the event that Merck exercises the global commercialization option, Merck will pay Abbisko an additional option exercising fee. The aggregate amounts of upfront payment, option exercising payment, and payment for development and commercialization milestones will total US$ 605.5 million. Abbisko will also receive double-digit percentage (%) royalties on annual net sales.

Pimicotinib is a novel, orally available, highly selective, and potent small molecule CSF-1R inhibitor, independently developed by Abbisko Therapeutics. It has been granted the Break Through Designation（BTD） and PRIME designation by China NMPA, U.S. FDA, and EMA for the treatment of TGCT patients who are not amenable to surgery. The study is the first global Phase III clinical trial of TGCT conducted simultaneously in China, the U.S., Canada and Europe.

Upon 1-year follow-up in a Phase 1b trial for TGCT, pimicotinib demonstrated an ORR of 87.5% (28/32, including 3 CR) in the 50 mg QD cohort，which was presented at the 2023 CTOS. Pimicotinib has completed a Phase I dose-escalation trial in the U.S. In December this year, it was granted Fast Track Designation (FTD) by the U.S. FDA for the treatment of unresectable TGCT .

In addition to TGCT, Abbisko is actively exploring the potential of pimicotinib in treating other indications including many types of solid tumors in clinic, and it has obtained approval from China NMPA to conduct Phase II clinical studies in chronic graft-versus-host disease (cGVHD) and advanced pancreatic cancer. Up until today, no highly selective CSF-1R inhibitors have been approved in China.

On January 8, 2024 Orion Corporation and Glykos Finland Oy reported that they have entered into a research collaboration and licensing agreement to develop next-generation antibody-drug conjugates (ADCs) (Press release, Orion, JAN 8, 2024, View Source [SID1234639115]).

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Under the agreement, Orion gains access to Glykos’ proprietary ADC technologies, initiating an ADC program with the potential for expansion into two additional programs in the future. Orion will be responsible for the target selection, research, development, and commercialization of up to three next-generation ADCs, with a focus on solid tumors.

Glykos is eligible for milestone payments related to signing of the agreement, target selection and sales milestones. Glykos is also entitled to receive royalties on commercial sales generated from the three ADC programs.

Outi Vaarala, Senior Vice President, Innovative Medicines and R&D, Orion, said: "Collaboration with Glykos and possibility to utilize their ADC technology complements nicely our research portfolio in oncology and is yet another demonstration of our will to develop new treatment options for cancer patients with unmet needs."

Juhani Saarinen, CEO of Glykos, said: "The acknowledgment of our ADC technology by an esteemed pharmaceutical company like Orion is a strong statement to the transformative potential of these technologies in enhancing the therapeutic index of ADCs. We look forward to partnering with Orion and believe that with their expertise on cancer therapies and robust clinical pipeline, this partnership can deliver innovative medicines for cancer patients."