On June 11, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported that Phase 1 clinical data of the globally first anti-CD47/PD-L1 bispecific antibody IBI322 for the treatment of anti-PD-(L)1-resistant patients with classic Hodgkin lymphoma was presented in oral presentation at the 28th Annual Meeting of the European Society of Hematology (EHA 2023) (Press release, Innovent Biologics, JUN 11, 2023, View Source [SID1234632627]). The EHA (Free EHA Whitepaper) Annual Meeting was held in Frankfurt, Germany, from June 8 to 15, 2023.

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Title: CD47/PD-L1 bispecific antibody (IBI322) in anti-PD-1 or PD-L1 treatment-resistant classical Hodgkin lymphoma: a Phase 1 study
Session: s445 Hodgkin lymphoma – Clinical, 11/06/2023, 11:30 – 12:45 (CEST)
Final Abstract Code: S216
Presenting Author: Dr. Jingwei Yu, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China

The presented data was based on an dose-expansion cohort from a Phase 1 study (NCT04795128) aiming to evaluate the safety and preliminary antitumor activity of IBI322 in patients with anti-PD-(L)1 treatment-resistant classic Hodgkin lymphoma. Eligible patients receive IBI322 (45 mg/kg intravenous Q2W) until unacceptable toxicity or disease progression, or up to 24 months. A total of 24 patients currently included, of which 23 patients were efficacy evaluable.

Among the 23 patients, the objective response rate (ORR) and disease control rate (DCR) were 47.8% (95% CI: 26.8-69.4) and 91.3% (95% CI: 72.0-98.9), respectively. Among the 7 patients with primary resistance, the ORR was as high as 57.1% (95% CI: 18.4-90.1), and 3 patients achieved complete response (CR).

In terms of safety, the incidence of treatment-related adverse reactions (TRAE) was 91.7%, and the most common TRAE were decreased lymphocyte count (62.5%), anemia (62.5%), decreased white blood cell count (20.8%), and decreased platelet count (20.8%). The incidence of grade ≥ 3 TRAE was 41.7%, with the most common ≥ grade 3 TRAE (>5%) associated with decreased lymphocyte count (29.2%). There were no TRAE leading to permanent treatment discontinuation or death. As of the data cut-off, 12 patients were still receiving IBI322 monotherapy.

Overall, IBI322 monotherapy showed promising anti-tumor efficacy with a manageable safety profile in anti-PD-1 or PD-L1 treatment-resistant classical Hodgkin lymphoma patients. Abstract Link

Professor Ting Niu, the principal investigator of this study, West China Hospital of Sichuan University, said: "This phase 1 study shows that IBI322 monotherapy is effective and safe in the treatment of PD-1 or PD-L1 treatment-resistant classical Hodgkin lymphoma, and we look forward to longer follow-up results and larger sample sizes in the future. IBI322 has the potential to be an effective treatment option for the treatment of immunotherapy-resistant classical Hodgkin lymphoma and other types of lymphoma to meet the unmet clinical needs. "

Dr. Hui Zhou, Senior Vice President of Innovent, said: "With the widespread application of anti-PD-(L)1 monoclonal antibodies in the field of classical Hodgkin lymphoma, immunotherapy resistance has emerged as an urgent clinical need. IBI322, as globally the first anti-CD47/PD-L1 bispecific antibody for the treatment of anti-PD-1 or PD-L1 treatment-resistant classic Hodgkin lymphoma, showed encouraging anti-tumor efficacy and a manageable safety profile in the Phase 1 clinical study, exhibiting its potential to overcome immunotherapy resistance for patients with classical Hodgkin lymphoma. "

About Hodgkin lymphoma

Hodgkin lymphoma is a special type of lymphoma containing Reed-Sternberg cells, which accounts for about 8.54% of lymphoma. The current incidence rate is about 0.6 cases per 100,000 population. After first-line radiotherapy + chemotherapy ABVD (doxorubicin + bleomycin + vincristine + dacarbazine), ASCT (autologous stem cell transplantation) has achieved a 5-year survival rate of more than 80% for patients, but the treated rate is limited in China due to several reasons, including the poor tolerability for certain patients, the relatively low mental acceptance, and limited medical resources; Another 15-20% of patients do not respond to initial treatment and develop relapsed or refractory classical Hodgkin lymphoma after immunotherapy resistance, which is currently an urgent clinical need.

About IBI322

IBI322 is a recombinant anti-human CD47/PD-L1 bispecific antibody developed by Innovent Biologics. As a bispecific antibody, IBI322 targets CD47 on the surface of tumor cells, blocks SIRPα/CD47 pathway and activates macrophages to attack the tumor cells. Furthermore, IBI322 target PD-L1 on the surface of tumor cells, blocks the PD-1/PD-L1 pathway, which counteracts the inhibition of T cells and activates the T cells to attack the tumor cells. By inhibiting two different targets, IBI322 can not only activate both innate immune pathway and adaptive immune pathway, which provides synergistic effect, but also reduce the red blood cell destruction.

On June 11, 2023 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported updated clinical data from KOMET-001, a Phase 1/2 clinical trial of the Company’s potent and selective menin inhibitor, ziftomenib, including significant clinical activity in patients with heavily pretreated and co-mutated relapsed/refractory NPM1-mutant acute myeloid leukemia (AML) (Press release, Kura Oncology, JUN 11, 2023, View Source [SID1234632626]).

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The updated clinical data are being featured during a late-breaking oral session today at the 2023 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in Frankfurt, Germany. A copy of the presentation is available in the Posters and Presentations section on Kura’s website.

"Our goal with our ziftomenib program is to transform the standard of care for patients with acute leukemias," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology, "and we are delighted to share new clinical and preclinical data that we believe further demonstrate its potential best-in-class product profile. The emerging data for ziftomenib include: high clinical activity in relapsed/refractory NPM1-mutant AML patients, including 35% achieving durable complete remissions (CR) with maintained full count recovery on ziftomenib monotherapy; a lower frequency of MEN1 resistance mutations; a favorable safety and tolerability profile; strong evidence of mechanistic synergy with standards of care such as venetoclax and FLT3 inhibitors; and convenient once-daily, oral dosing and optimal pharmaceutical properties for combination. We believe ziftomenib has the ideal properties to become a cornerstone of therapy across the continuum of treatment, and we intend to build on the growing momentum as we continue to execute on our registration-enabling study in NPM1-mutant AML and move rapidly into combinations."

As of the data cutoff on April 12, 2023, seven of the 20 patients (35%) with NPM1-mutant AML treated at the recommended Phase 2 dose (RP2D) of 600 mg achieved a CR with full count recovery. Notably, 33% (2/6) of patients with FLT3 co-mutations and 50% (4/8) of patients with IDH co-mutations achieved a CR on ziftomenib. Two patients underwent a stem cell transplant (SCT) and remain in remission as of the data cutoff, including one on post-SCT ziftomenib maintenance therapy. An eighth patient who had a CR with incomplete recovery (CRi) at the time of transplant subsequently evolved to a CR and remains on study.

The median duration of response for all NPM1-mutant patients was 8.2 months (95% CI: 1.0 to NE), with a median follow-up of 8.8 months. The median duration of response for patients censored at SCT was 5.6 months (95% CI: 1.0 to NE). As of the cutoff date, three patients treated at 600 mg remain on study and in CR; an additional NPM1-mutant patient treated at 200 mg remained on ziftomenib for 36 cycles.

As part of an ongoing analysis, the resistance mutation MEN1-M3271 has been detected in three patients treated with ziftomenib: in two patients, the mutation was detected at study entry after the patients had progressed on a prior menin inhibitor, and in the third patient, the mutation was detected after four cycles of ziftomenib therapy and, despite the mutation, the patient was maintained in a condition of stable disease through cycle 7. These data show that MEN1 mutations developed in just 3% (1/29) of patients analyzed following treatment with ziftomenib and suggest that resistance mutations are less likely to evolve after prolonged exposure to ziftomenib monotherapy. A key new biochemical finding, confirmed by crystal structure, demonstrates that ziftomenib retains full activity against the MEN1-T349M mutation, detected in two-thirds of patients who acquired menin resistance mutations on another recent menin inhibitor trial.

"NPM1-mutant AML accounts for approximately 30% of AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists," said Amir Fathi, M.D., Director of the Leukemia Program at the Massachusetts General Hospital. "The clinical data presented today continue to demonstrate the ability of ziftomenib to drive durable responses as a monotherapy in heavily pretreated patients with NPM1-mutant AML. In addition, data appears to suggest that ziftomenib is less likely to induce common MEN1 resistance mutations, coupled with emerging data showing the retention of activity against other key resistance mutants, are exciting, as we look to advance ziftomenib into combinations and treat patients in earlier lines of therapy."

Continuous daily dosing of ziftomenib was well tolerated and the safety profile remains consistent with features of underlying disease. The on-target effect of differentiation syndrome was manageable, with 15% of patients experiencing Grade 1 or 2 events and 5% experiencing a Grade 3 event.

Enrollment in a Phase 2 registration-directed study of ziftomenib in patients with relapsed/refractory NPM1-mutant AML continues to outperform projections. The study is expected to enroll a total of 85 patients at 62 U.S. and European sites. Kura is also preparing to initiate a series of studies to evaluate ziftomenib in combination with current standards of care in earlier lines of therapy and across multiple patient populations, including NPM1-mutant and KMT2A-rearranged AML. The Company has begun site activation in the first of these studies, KOMET-007, and is on track to dose the first patients this quarter.

Virtual Investor Event

Management will host a virtual investor event featuring company management and investigators from the Phase 1 trial of ziftomenib at 8:00 a.m. ET on Monday, June 12, 2023. The event will be webcast live and can be accessed on the Investors section of Kura’s website at www.kuraoncology.com. An archived replay will be available shortly after the conclusion of the live event.

About Acute Myeloid Leukemia

AML is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor. NPM1-mutations are among the most common genetic alterations, representing approximately 30% of AML cases. While patients with NPM1-mutant AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30% overall survival at 12 months in the relapsed or refractory setting. Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the occurrence of co-occurring mutations. Median overall survival is only approximately six months following relapse for NPM1-mutant patients. KMT2A-rearrangements are less frequent, representing approximately 5-10% of AML. No FDA-approved therapies targeting NPM1-mutant and KMT2A-rearranged AML currently exist.

About Ziftomenib

Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need. In preclinical models, ziftomenib inhibits the KMT2A/MLL protein complex and exhibits downstream effects on HOXA9/MEIS1 expression and potent anti-leukemic activity in genetically defined preclinical models of AML. Ziftomenib has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.

On June 10, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that updated preclinical data on its IPH6501 tetra-specific ANKET (Antibody-based Natural Killer cell Engager Therapeutics) are presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 congress (Press release, Innate Pharma, JUN 10, 2023, View Source [SID1234632625]). IPH6501 is a first-in-class CD20-targeting tetra-specific ANKET that co-engages two activating receptors (NKp46 and CD16), the interleukin-2 receptor (without involvement of the IL-2Rα subunit) with a human IL-2 variant and CD20 target antigen on malignant B cells.

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In preclinical settings, IPH6501 was shown to induce NK cell proliferation and to trigger high NK cell cytoxicity against CD20+ target cells in in vitro assays, in ex vivo assays with relapse/refractory (R/R) B-NHL patient samples who received at least one prior treatment, as well as in in vivo studies in non-human primates. A surrogate of IPH6501 mediated a potent anti-tumor activity in vivo in CD20+ tumor models in mice. In addition, in ex vivo assays with R/R B-NHL patient samples, IPH6501 was shown to be more efficient than a T cell engager targeting CD20.

Pr. Eric Vivier, PhD, DVM, Chief Scientific Officer at Innate Pharma "As the lead in this new class of tetra-specific NK-cell engager, IPH6501 represents an innovative option for the treatment of R/R B-cell non-Hodgkin’s lymphomas after multiple lines of treatment, who are still in need of therapies. By providing proliferation and activation signals targeted to NK cells, the tetra-specific NK Cell Engager based on our ANKET platform leverages the advantages of harnessing NK cell effector functions against cancer cells. With a low systemic cytokine release profile, IPH6501 represents a promising alternative strategy to T cell therapies. IPH6501 continues to progress towards a Phase 1 clinical trial and we look forward to share further updates on other ANKET assets as they enter clinic."

About ANKET

ANKET is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer. This fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer.

Innate’s latest innovation, the tetra-specific ANKET, is the first NK cell engager technology to engage activating receptors (NKp46 and CD16), a tumor antigen and the interleukin-2 receptor (via an non-alpha IL-2 variant, IL-2v) via a single molecule. By providing proliferation and activation signals targeted to NK cells, tetra-specific ANKET leverages the advantages of harnessing NK cell effector functions against cancer cells.

On June 10, 2023 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral kinase inhibitors to treat hematologic malignancies, reported highlights from a clinical update event held today, June 10, 2023, in conjunction with EHA (Free EHA Whitepaper) 2023 International Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Frankfurt, Germany (Press release, Aptose Biosciences, JUN 10, 2023, View Source [SID1234632619]). The event included an up-to-date review of clinical data for Aptose’s two investigational products under development for hematologic malignancies: tuspetinib, an oral, myeloid kinase inhibitor in the Phase 1/2 APTIVATE trial in patients with relapsed or refractory acute myeloid leukemia (AML); and luxeptinib, an oral, dual lymphoid and myeloid kinase inhibitor in Phase 1 a/b stage development for the treatment of patients with relapsed or refractory hematologic malignancies. The webcast of the presentation is available on Aptose’s website here.

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Aptose provided updated clinical findings with tuspetinib, a potent suppressor of FLT3, SYK, JAK 1/2, mutant forms of cKIT, and the RSK1/2 kinases operative in AML:

Completed tuspetinib dose escalation and dose exploration Phase 1/2 trial in 77 R/R AML patients.
Tuspetinib demonstrated a favorable safety profile.
Tuspetinib delivered monotherapy responses across four dose levels with no DLT in mutationally diverse and difficult to treat R/R AML populations, including TP53-mutated patients with a CR/CRh = 20% and RAS-mutated patients with a CR/CRh = 22%.
Completed successful End of Phase 1 (EOP1) Meeting with US FDA for tuspetinib, and a monotherapy RP2D was selected as 80mg daily, and all development paths remain open, including the single arm accelerated path.
Initiated tuspetinib APTIVATE expansion trial with R/R AML patients.
Tuspetinib is being administered as a monotherapy and as a combination doublet with tuspetinib + venetoclax (TUS/VEN), and enrollment has been brisk.
TUS/VEN doublet has been well tolerated, all patients remain on study, and preliminary CR activity has already been reported in patients previously treated with VEN.
Aptose also reviewed clinical findings with the new G3 formulation of luxeptinib (Lux):

50mg G3 formulation with continuous dosing achieves roughly equivalent PK profile as 900mg original G1 formulation.
Expect to dose escalate G3 formulation with continuous dosing in patients soon.
"We are delighted to have finalized our dose escalation and dose exploration Phase 1/2 trial with tuspetinib (TUS), to have demonstrated single agent responses across four dose levels that had no DLTs and across a range of R/R AML populations with a diversity of adverse mutations," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "As part of our EOP1 meeting with the FDA, we designated 80mg daily as our monotherapy recommended phase 2 dose (RP2D), and now we focus all attention on our APTIVATE expansion trial to place monotherapy TUS in more patients with highly adverse mutations and to evaluate TUS in combination with venetoclax (VEN) as a doublet in R/R AML patients. Notably, to date, the doublet appears to be well tolerated, with all patients remaining on study, including a preliminary CR in a R/R AML patient who previously failed venetoclax. We look forward to accelerating testing of the doublet, adding MDS patients to our APTIVATE trial, and with the aim of moving into triplet therapy (TUS/VEN/HMA) in 1L AML patients."

On June 10, 2023 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported presentations highlighting preliminary data based on a November 2022 data cut-off from its Phase 1 dose escalation clinical trial of NKX019 at two scientific conferences: the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Hybrid Congress and the 17TH International Conference on Malignant Lymphoma (17-ICML) (Press release, Nkarta, JUN 10, 2023, View Source [SID1234632614]). NKX019 is an allogeneic, off-the-shelf NK cell therapy candidate derived from healthy donors and engineered to target CD19.

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Seven of ten patients with relapsed/ refractory non-Hodgkin lymphoma (NHL) treated at the higher dose levels showed a complete response (70% CR), including two patients with aggressive large B cell lymphoma (LBCL) as well as other difficult histologies, including mantle cell lymphoma (MCL), high-risk follicular lymphoma (FL) and marginal zone lymphoma (MZL). No dose limiting toxicity, neurotoxicity / ICANS, graft versus host disease (GvHD), or >Grade 3 cytokine release syndrome (CRS) were observed in the study.

"Autologous CAR-T cell therapies set a standard for responses in patients with relapsed/ refractory B-cell malignancies. However, potential for toxicity and logistic challenges have limited access to these therapies, and many patients could still benefit from a safe, on-demand treatment," said Michael Dickinson, M.D., Lead, Aggressive Lymphoma disease group, Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, and investigator in the NKX019 trial. "In this early evaluation of an allogeneic CAR-NK cell therapy candidate, NKX019 had a manageable safety profile with encouraging anti-tumor activity as well as the option for retreatment after relapse. Based on these early data, NKX019 merits further study as a potential outpatient cell therapy approach."

"These data highlight the encouraging safety profile and clinical activity across different histologies in the dose escalation portion of the NKX019 study," said David R. Shook, M.D., Nkarta’s Chief Medical Officer. "We continue to explore the potential of allogeneic CAR NK cells, leveraging their biology to create a differentiated cellular therapy, and we look forward to the next update on the NKX019 program later this year."

Nkarta’s presentation materials from EHA (Free EHA Whitepaper) and ICML will be available for download on the Nkarta website (View Source). The presentations will ensure that the broader clinical and academic community has the opportunity to assess the NKX019 clinical data in a peer-reviewed format. All data were previously disclosed at a company event in December 2022. Nkarta plans to provide an update from the NKX019 program, including data from dose expansion cohorts, in 2023.

About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies. To learn more about the NKX019 clinical trial in adults with advanced B cell malignancies, please visit ClinicalTrials.gov.