On July 27, 2023 Synthekine Inc., a leader in engineered cytokine therapeutics, reported that the first patient has been dosed in a Phase 1 clinical trial of its orthogonal IL-2 and CD19 CAR-T combination therapy, STK-009 + SYNCAR-001, in adults with relapsed or refractory CD19+ hematologic malignancies (Press release, Synthekine, JUL 27, 2023, View Source [SID1234633473]). STK-009 + SYNCAR-001 is a two-component therapy consisting of SYNCAR-001, a CD19-targeting chimeric antigen receptor T cell (CAR-T) which expresses an engineered IL-2 receptor allowing it to selectively receive a signal from STK-009, an engineered pegylated IL-2 cytokine.

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"SYNCAR-001 + STK-009 is our second clinical stage program at Synthekine and represents another key milestone in our journey to develop novel cytokine therapeutics for patients with refractory cancers," said Debanjan Ray, chief executive officer of Synthekine. "Our orthogonal IL-2 system is a unique platform that breaks new ground in the field of cell therapy. Combining STK-009 with SYNCAR-001 has the potential to overcome key limitations associated with current CD19 CAR-T cell therapies, such as poor expansion and limited persistence following T cell transfer. These limitations have been shown to correlate with poor response and relapse, particularly in challenging hematological malignancies. We look forward to further evaluating STK-009’s ability to offer a safer approach with improved efficacy and durability."

Published results from preclinical studies show that treatment with STK-009 resulted in both systemic and intratumoral expansion and activation of SYNCAR-001 cells. As a result, even with substantially reduced cell doses, SYNCAR-001 together with STK-009 treatment was able to drive complete responses in large lymphoma tumors in preclinical models.

"While CAR-T cell therapies have had a major impact for patients with CD19+ hematologic malignancies, only a subset of these patients have durable benefit," said Naiyer Rizvi, M.D., chief medical officer of Synthekine. "We believe that controllable, selective and sustained cytokine support is central to the advancement of this class of treatment, and STK-009 + SYNCAR-001 has the potential to drive deeper and more durable responses while avoiding serious toxicities related to uncontrolled CAR-T cell expansion for patients in need of better treatment options."

The first-in-human Phase 1 clinical trial of SYNCAR-001 + STK-009 is an open-label, multi-center study enrolling patients with CD19+ hematologic malignancies. For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT05665062.

On July 27, 2023 Cellinfinity Bio, a privately held biotechnology company developing first/best-in-class cell therapy products against solid tumors and other diseases, reported the publication of a novel CAR enhancement, the addition of CTLA-4 intracellular domain to improve anti-tumor CAR-T activity (Press release, Cellinfinity Bio, JUL 27, 2023, View Source [SID1234633472]). This technology is published in Nature Immunology on July 27. Trogocytosis is a process where cancer antigens are transferred onto immune cells, including T-cells; if the cancer antigen is a target of CAR-Ts, this results in CAR-Ts killing each other or fratricide. The addition of intracellular domain of CTLA-4 prevented trogocytosis and resulted in improved CAR-T survival, including maintenance of central memory T-cells and increased T-cell persistence – all leading to stronger anti-tumor efficacy. Cellinfinity Bio has an exclusive license of the published CTLA-4 tail technology from Yale University and Professor Sidi Chen’s lab, Founder of Cellinfinity Bio and Associate Professor of Genetics, Yale University.

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"Trogocytosis and fratricide substantially limit current CAR-T cell therapy response. We found a portion of CTLA-4 intracellular domain when fused onto CAR sequence optimizes CAR-T function and results in low trogocytosis, greater durability, and more potent in vitro and in vivo anti-tumor efficacy," said Sidi Chen. "Furthermore, the simple addition of CTLA-4 tail onto CARs has potential to improve CAR-Ts against diverse targets."

"Cellinfinity has identified several important gene enhancements and CAR modifications that improve anti-tumor activity of adoptive cell therapy," added Premal Patel, M.D., Ph.D., Chief Executive Officer, Cellinfinity Bio. "We intend to evaluate this CTLA-4 tail technology across diverse next generation of CAR-Ts targeting variety of cancers." Cellinfinity holds exclusive rights to the CTLA-4 tail technology, as well as exclusive license to other novel cell evolution technologies from the Chen lab at Yale University, that allow whole-genome gain-of-function and loss-of-function genetic screens.

On July 27, 2023 Cullgen Inc., a leading biotechnology company developing small molecule therapeutics based on its proprietary uSMITE platform of targeted protein degradation technology, reported that it has initiated dosing with its orally bioavailable pan-TRK degrader, CG001419, in a Phase I/II clinical trial for patients with solid tumors (Press release, Cullgen, JUL 27, 2023, View Source [SID1234633471]). CG001419 is a potential first-in-class, highly active small molecule developed to selectively degrade both mutant and wild-type TRK proteins. In preclinical research, CG001419 demonstrated strong potency against solid tumors harboring various oncogenic TRK abnormalities, such as NTRK gene fusions and wild-type TRK protein over-expression.

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"We are excited to initiate human dosing for CG001419," said Dr. Ying Luo, Chairman and CEO of Cullgen, "This is a significant milestone for Cullgen as it marks our first entry into the clinic for one of our targeted protein degraders. I am very proud of the progress that our entire company has made to advance our first program into the clinic in only a few years since inception of the program."

The first-in-human trial of CG001419 is a Phase I/II trial with adaptive design. The Phase Ia portion of the trial is an open label, non-randomized, dose escalation study to evaluate the safety, tolerability, PK profile, and preliminary efficacy of CG001419 in patients with advanced or metastatic solid tumors, particularly those harboring NTRK gene fusions, point mutations, amplifications or over-expression. Patients that complete the Phase Ia trial may transition into the Phase Ib or Phase II portions of the trial depending on safety and tolerability results, the patient’s NTRK aberration type, and the judgment of physicians. Compared with traditional kinase inhibitor drugs approved in treating cancer with NTRK gene fusions, CG001419 may offer potential advantages in overcoming secondary drug-resistant mutations in NTRK fusions, as well as an expanded clinical profile to include cancers with other NTRK gene/TRK protein abnormalities.

On July 27, 2023 DELFI Diagnostics, a pioneering developer of a new class of high-performance, accessible liquid biopsy tests for early cancer detection and monitoring, reported to have licensed a new, highly accurate method for identifying somatic genomic alterations in cell-free DNA (cfDNA) known as GEMINI, or GEnome-wide Mutational Incidence for Non Invasive detection of cancer (Press release, Delfi Diagnostics, JUL 27, 2023, View Source [SID1234633470]).

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Until now, first-generation liquid biopsy technologies relied on expensive, deep, targeted sequencing to detect mutations associated with cancer. Now, for the first time, researchers have achieved genome-wide detection of tumor-specific mutations from the same low-coverage whole genome sequencing methods that form the basis of the DELFI Diagnostics platform.

In a study published today in Nature Genetics, researchers showed that GEMINI, combined with the approach used by DELFI Diagnostics, could successfully identify early stage lung cancers – those cancers that are most critical to detect to change patient outcome. In a cohort of lung cancer cases and non-cancer controls (n=163), combining the GEMINI analysis with DELFI’s fragmentomics approach yielded an area under the receiver operator curve (AUC), a common measure of diagnostic accuracy, of 0.931. The combined technology also showed high performance in other applications including monitoring response to therapy, and distinguishing small-cell lung cancer from non-small cell lung cancer.

"We founded DELFI Diagnostics to address population-health needs in cancer detection with low-cost, flexibly deployable technology," said Nicholas Dracopoli, PhD, DELFI Diagnostics’s Chief Scientific Officer and Co-Founder. "Whenever we evaluate new technology, it must meet multiple criteria: It must help boost early stage cancer detection, and it must be able to be applied to the sequencing data generated from our low-cost platform. GEMINI fulfills both those requirements and shows how we can further refine the performance of our platform without changing our lab processes."

DELFI Diagnostics’s fragmentomics-based approach applies machine learning-based algorithms to low-coverage, whole genome sequencing data from cfDNA. Beyond the genome-wide analysis of fragment length profiles that reflect the aberrant packaging of DNA in cancer cells, the whole-genome sequencing approach also reveals many other changes in DNA features including somatic genomic alterations, amplifications, deletions, and more.

"We have already shown that this platform can detect lung cancer with very high sensitivity," said Peter Bach, MD, DELFI Diagnostics’s Chief Medical Officer. "This new study shows that what was a first-generation approach to cancer detection — looking for genomic mutations — can now be extended genome-wide and enhanced with the DELFI platform, improving early stage cancer detection with no additional sequencing or lab prep cost."

On July 27, 2023 HanAll Biopharma Co., Ltd. (KRX: 009420. KS), a global biopharmaceutical company committed to discovering and developing innovative medicines for patients, reported financial results for the second quarter and provided business updates (Press release, HanAll Biopharma, JUL 27, 2023, View Source [SID1234633469]).

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HanAll ended the quarter with total revenue of 41.4 billion won, an increase of 58 percent compared to the same period last year, and an operating profit of 8.1 billion won. Net profit recorded 7.3 billion won due to the continued growth of its pharmaceutical products and milestone revenues from the licensed partner.

"We are pleased to announce another successful quarter with strong sales growth and significant advancements in clinical developments. We achieved a meaningful result from the tanfanercept Phase 3 study for dry eye disease, while batoclimab progressed another step further towards commercialization in China. Our commitment to innovation is evident by portfolio expansion and fruitful collaborations in the neurodegenerative domain," said Sean Jeong, M.D., MBA, CEO of HanAll Biopharma.

"In the second half 2023, we anticipate the initiation of a Phase 1 clinical study on Parkinson’s disease (PD), along with the initial results from the anti-FcRn assets batoclimab in Grave’s disease and Phase 1 study of HL161ANS. In addition, we anticipate finalizing the next Phase 3 clinical study design for tanfanercept this year. These upcoming milestones exemplify our dedication to advancing innovative medicines, and we will continue to push the boundaries of science and steadfastly pursue our mission to improve patient outcomes," he added.

SECOND QUARTER 2023 BUSINESS UPDATE
Pipeline Development Highlights
A comprehensive update of HanAll’s pipeline development below includes an overview of research along with lists of compounds, targeted indications, and developmental phase.

AUTOIMMUNE DISEASES PROGRAMS
Batoclimab (HL161BKN)
A novel, fully human, subcutaneously administered antibody targeting FcRn with the potential to address multiple IgG-mediated autoimmune diseases. Batoclimab is designed to selectively bind to and inhibit FcRn, which plays a role in recycling IgG, thus may reduce harmful IgG antibodies.

Harbour BioMed, a licensed partner of HanAll in China, announced the official acceptance of the Biologics License Application (BLA) for batoclimab for the treatment of generalized myasthenia gravis (gMG) in June 2023, based on the positive topline result from the Phase 3 clinical trial in early March this year. The data from the Phase 3 clinical trial met the primary efficacy endpoint as well as key secondary endpoints with a favorable profile. Batoclimab received the ‘Breakthrough Therapy Certificate’ from NMPA in 2021.
Another licensed partner, Immunovant, located in the U.S. and Europe, is currently carrying out global Phase 3 trials on batoclimab in both gMG and TED. The initial results from the Phase 2 trial evaluating batoclimab in Grave’s disease (GD), is expected in the fourth quarter of 2023. The company expects initial results from the pivotal Phase 2b trial of CIDP in the first half of 2024.
HanAll is progressing towards the initiation of a Phase 3 clinical study of batoclimab in gMG in Japan this year. Additionally, HanAll is exploring options for developing batoclimab for TED and chronic inflammatory demyelinating polyneuropathy (CIDP) in Japan.
HL161ANS
Another novel, fully human, subcutaneous antibody molecule that inhibits FcRn-mediated recycling of IgG is designed to deliver maximum lgG reductions while minimizing interference with albumin recycling.

Immunovant is progressing a Phase 1 clinical trial of HL161ANS, a new FcRn inhibitor (Immunovatnt project designation: IMVT-1402), in New Zealand to evaluate the safety, pharmacokinetics, and pharmacodynamics profile in healthy patients. The Initial data readout for single-ascending dose (SAD) cohorts is expected in third quarter of 2023, and multi-ascending dose (MAD) cohorts are expected in the fourth quarter of 2023. Immunovant also received IND clearance for HL161ANS from the U.S. Food and Drug Administration (FDA) in the second quarter of 2023.
OPHTHALMIC DISEASE PROGRAMS
Tanfanercept (HL036)
A novel topical protein therapy for ophthalmic diseases, including dry eye disease (DED), which inhibits TNF alpha, a key mediator of ocular inflammation

HanAll Biopharma and Daewoong Pharmaceutical announced the top-line results from the Phase 3 VELOS-3 trial evaluating tanfanercept ophthalmic solution for the treatment of DED in May 2023. The Phase 3 VELOS-3 did not demonstrate statistical significance in either of the primary outcome measures of improvement in central corneal staining score (CCSS) or improvement in Eye Dryness Score (EDS) assessed at week 8 in subjects with moderate to severe DED. However, the solution demonstrated a highly statistically significant improvement in the secondary efficacy endpoint of the unanesthesized Schirmer test evaluating the change in tear volume from baseline in patients treated with tanfanercept compared to the vehicle arm assessed at week 8. HanAll and Daewoong plan to finalize the next study design within the second half of 2023 and intend to discuss VELOS-3 data and future plans with the FDA, with plans to begin the next study in the first half of 2024.
Previous notices reflected a significant improvement of p < 0.001 in the secondary efficacy endpoint of unanesthesized Schirmer testing to quantify change from baseline in tear volume in tanfanercept treatment arm relative to vehicle arm assessed at week 8 as well as a statistically different rate of the proportion of subjects whose Schirmer test improved from baseline by 10mm or greater at week 8 in tanfanercept arm (15%) relative to vehicle arm (4%), p < 0.001. Further analyses have revealed an update to those percentages and to the p-values, although there are no interpretation changes. The secondary efficacy endpoint of unanesthesized Schirmer testing to quantify the change from baseline in tear volume in tanfanercept treatment arm relative to vehicle arm assessed at week 8 demonstrated a significant improvement (p = 0.002). Additionally, the proportion of subjects whose Schirmer test improved from baseline by 10mm or greater as assessed at week 8 was statistically significant (p = 0.011) in the tanfanercept arm (13%) relative to the vehicle arm (4%).
Harbour BioMed, a licensed partner of HanAll in China, is discussing further development plans for tanfanercept in China.
ONCOLOGY PROGRAMS
HL187/ HL186
Monoclonal antibodies that respectively target T cell immunoreceptors with immunoglobulin (Ig) and ITIM (Immunoreceptor tyrosine-based inhibitory moti)} domains (TIGIT) and T cell Ig and mucin domain-3 (TIM-3) are being developed in collaboration with Daewoong Pharmaceutical as potential oncology treatments

HanAll is continuing with the pre-clinical development of the HL187 (anti-TIGIT) asset and plans to evaluate the further development of HL186 (anti-TIM-3) based on the strategic portfolio review.
NEUROLOGY PROGRAMS
HL192
A pipeline candidate originated from NurrOn Pharmaceuticals that targets Nurr1, a master regulator in dopaminergic neuron development and maintenance, is being developed to treat neurodegenerative diseases, including Parkinson’s disease (PD)

HanAll entered into joint clinical development with NurrOn Pharmaceuticals and Daewoong Pharmaceutical to develop NurrOn’s leading asset HL192 (NurrOn project designation: ATH-399A) which will be evaluated in an array of neurodegenerative diseases with the primary area of focus targeting PD. The Phase 1 clinical study of HL192 in healthy participants is expected to be initiated this year.
FINANCIAL HIGHLIGHTS (CONSOLIDATED)
Key Highlights

(KRW in billion)

Q2 2023

Q2 2022

% change

Sales

41.4

26.2

+58 %

Gross Profit

27.2

14.9

+82 %

Selling, marketing and administrative expenses

11.3

10.6

+7 %

Research and development expenses

7.8

3.7

+111 %

Operating income

8.1

0.7

+1092 %

Net Income

7.3

(0.1)

N/A

Sales recorded 41.4 billion won in the second quarter of 2023, a 58 percent increase compared to the second quarter of 2022. Strong sales growth from pharmaceuticals continued from major products sold under the names of Biotop, Eligard, and Normix, with Biotop recording sales growth of 70% compared to the same period last year.

Research and development expenses for the second quarter ended June 30, 2023, were 7.8 billion won, up 111 percent from 3.7 billion won for the three months ended June 30, 2022.

Net income for the three months ended June 30, 2023, recorded 7.3 billion won, due to an increase in milestone revenue and pharmaceutical sales.