On December 11, 2023 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported data from multiple trials of revumenib in combination with standard of care agents in patients with nucleophosmin mutant (mNPM1) and KMT2A-rearranged (KMT2r) relapsed/refractory (R/R) acute leukemias (Press release, Syndax, DEC 11, 2023, View Source [SID1234638437]). Revumenib is the Company’s highly selective, oral menin inhibitor.

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Data to date demonstrate that revumenib has been well tolerated and demonstrated clinical activity in combination with venetoclax/hypomethylating agents in both the frontline and R/R acute myeloid leukemia (AML) settings, as well as in combination with fludarabine/cytarabine (FLA) chemotherapy in a heavily pretreated R/R pediatric AML population, including in patients who relapsed on FLA. In all three trials, patients are now receiving the full monotherapy recommended Phase 2 dose in combination with the standard of care agents. The new combination data collectively highlight revumenib’s potential to safely combine with current standard of care agents across the acute leukemia treatment landscape, and support expansion of ongoing trials and advancement into additional combination trials currently in planning.

"Given the urgent need for novel, effective solutions for acute leukemia patients, we’re excited to show clinical data demonstrating tolerability and compelling clinical responses when revumenib is added to current treatment regimens," said Michael A. Metzger, Chief Executive Officer. "The potential to safely combine with standard of care positions revumenib to become a cornerstone of treatment across a range of acute leukemia populations. In addition, current response rates seen across all three trials strengthen revumenib’s already robust clinical profile as a monotherapy and furthers our conviction that revumenib could be a first- and best-in-class treatment for both KMT2Ar and mNPM1 acute leukemias."

SAVE AML Trial

Results from the SAVE AML trial of revumenib in combination with venetoclax-decitabine/cedazuridine in R/R AML were featured during an oral session at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The dose escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg every 12 hours (q12h) in combination with azole antifungals known to strongly inhibit CYP3A4 enzymes. As of a data cutoff date of November 1, 2023, nine patients with KMT2Ar, mNPM1 or NUP98r AML or mixed phenotypic acute leukemia (MPAL) were enrolled and response evaluable at the time of the data cut. Patients received a median of three prior lines of therapy, including 56% who received prior venetoclax and 67% who received prior hypomethylating agents (HMA) or underwent prior stem cell transplant or both.

All nine patients attained a morphologic remission for an overall response rate of 100%, 78% of whom achieved a CRc1 including 44% who achieved a CR/CRh. 67% (6/9) of patients in the trial attained minimal residual disease (MRD) negative status. Five patients transitioned to hematopoietic stem-cell transplantation (HSCT) following response. Two patients initiated post-transplant maintenance with revumenib and continue in remission for over 11 months.

The combination was well tolerated in this relapsed and refractory population, with no new safety signals observed beyond those reported for venetoclax-HMA. Grade ≥3 treatment related adverse events (TRAEs) included febrile neutropenia (56%), decreased platelets count (22%), decreased neutrophil count (22%) and lung infection (22%). There was one dose-limiting toxicity (DLT) at each dose level, Grade 4 thrombocytopenia that resolved after a dosing hold. There were no deaths due to TRAEs and no Grade 3 or higher QTc prolongation occurred.

BEAT AML Trial

The Company also announced data from the BEAT AML trial of revumenib in combination with venetoclax/azacitidine in newly diagnosed mNPM1 or KMT2Ar AML patients. The dose escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg q12h in combination with azole antifungals known to strongly inhibit CYP3A4 enzymes. As of the data cutoff date of December 1, 2023, 13 newly diagnosed mNPM1 (n=8) or KMT2Ar (n=5) AML patients were efficacy evaluable. In the efficacy evaluable population, the CRc was 100% (13/13) after 1 – 2 cycles of induction. Eleven (85%) of 13 patients attained a CR/CRh and 92% (12/13) attained MRD negative status. Two patients proceeded to transplant.

No new safety signals were identified when revumenib was added to the standard venetoclax/azacitidine doublet in newly diagnosed AML patients. One patient at the lowest dose level, 113 mg q12h, experienced a DLT of decreased platelet counts; no DLTs were observed in the 163 mg q12h dose cohort. 31% of patients experienced differentiation syndrome or QTc prolongation, each included one (8%) Grade 3 event. All were managed without dose reductions. Cytopenias were manageable across the treatment experience with continuous dosing of venetoclax and revumenib. There were no increased safety issues outside of known adverse events reported for venetoclax/azacitidine toxicities.

An expansion cohort is planned to further evaluate safety and activity of this combination, and the full BEAT AML data will be presented at a future medical conference.

AUGMENT-102 Trial

The Company announced data from the AUGMENT-102 trial of revumenib in combination with fludarabine/cytarabine in a predominantly pediatric relapsed/refractory mNPM1 (n=1), NUP98r (n=1) and KMT2Ar (n=13) AML population. The dose-escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg every 12 hours in combination with azole antifungals known to strongly inhibit CYP3A4 enzymes. As of the data cutoff date of September 20, 2023, 15 AML patients were efficacy evaluable, including three patients treated at 113 mg q12h and 12 patients treated at 163 mg q12h. The 163 mg q12hr cohort was comprised of primarily pediatric patients (median age of four), who had received a median of four prior lines of therapy. Across both dose groups, 50% of patients had failed prior treatment with fludarabine/cytarabine. Among the 12 patients treated at 163 mg q12h, four (33%) patients achieved a CRc including three (25%) patients that achieved a CR; four (33%) proceeded to transplant, including one mNPM1 patient who received a five-day course of decitabine prior to transplant.

The triplet of revumenib-fludarabine-cytarabine had an adverse event profile consistent with that observed with fludarabine-cytarabine alone, and no new safety signals were identified in the trial. Grade ≥3 TRAEs in over 30% of patients included decreased platelets (53%), decreased white blood cells (40%) and anemia (33%).

Copies of the ASH (Free ASH Whitepaper) presentations are available in the Publications and Meeting Presentations section of Syndax’s website.

Syndax Corporate Event

The above combination data, along with other data presented through today at the 65th ASH (Free ASH Whitepaper) Annual Meeting being held in San Diego, CA for both the revumenib and axatilimab clinical programs, will be highlighted at the Company’s investor event on Monday, December 11, 2023 at 7:00 a.m. PT/10:00 a.m. ET. The live audio webcast and accompanying slides for the event may be accessed through the Events & Presentations page in the Investors section of the Company’s website or directly through the meeting link here.

For those unable to participate in the conference call or webcast for the event, a replay will be available on the Investors section of the Company’s website at www.syndax.com for a limited time.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted BTD by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement. Syndax expects to complete an NDA submission for KMT2Ar acute leukemia under the Oncology Center of Excellence Review RTOR Program by year-end 2023.

About KMT2A (MLL) Rearranged Acute Leukemia

Rearrangements of the KMT2A (mixed lineage leukemia or MLL) gene give rise to KMT2Ar acute leukemia that is known to have a poor prognosis. KMT2A genes produce fusion proteins that require interaction with the protein called menin to drive leukemic cancer growth. Disruption of the menin-KMT2Ar interaction has been shown to halt the growth of KMT2Ar leukemic cells. KMT2Ar acute leukemia can phenotypically appear as AML, ALL, or mixed phenotype acute leukemia (MPAL) and is routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques. The median overall survival (OS) after standard of care first-line treatment, including intensive chemotherapy and transplant, is less than one year and the majority of patients suffer relapse within five years. With third line treatment or beyond, less than 5% of patients achieve complete remission (CR), and the median OS is less than three months. There are currently no approved therapies indicated for KMT2A-rearranged acute leukemia.

About NPM1-Mutant Acute Myeloid Leukemia

NPM1-mutant AML, which is distinguished by mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases. This subtype of AML has a five-year overall survival rate of approximately 50%. Similar to KMT2A- rearranged acute leukemia, NPM1-mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-KMT2A interaction. NPM1-mutant AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies indicated for NPM1-mutant AML.

On December 11, 2023 IASO biotechnology ("IASO Bio"), a biopharmaceutical company engaged in discovering, developing, manufacturing and marketing innovative cell therapies and antibody products, and Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune, ophthalmology and other major diseases, reported the latest analysis results from the FUMANBA-1 study of Equecabtagene Autoleucel for the treatment of multiple myeloma in an oral presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, IASO Biotherapeutics, DEC 11, 2023, View Source [SID1234638454]). The presentation highlights the characteristics and efficacy of fully human BCMA-targeting CAR-T (Equecabtagene Autoleucel) on multiple myeloma patients who had sustained minimal residual disease (MRD) negativity after receiving treatment.

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Oral Presentation Overview

Presentation Title: Efficacy Outcomes and Characteristics of Patients with Multiple Myeloma (MM) Who Achieved Sustained Minimal Residual Disease Negativity after Treatment with Equecabtagene Autoleucel (Eque-cel, CT103A) in Fumanba-1

Session Date and Time: Monday, December 11, 2023, 11:30 AM (San Diego)

Publication Number: 761

Presenter: Dr. Jue Wang, Associate Professor, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

The presentation is based on a post-hoc analysis of the FUMANBA-1 study. The FUMANBA-1 Study(Registration No.: NCT05066646) is a Phase Ib/II, single-arm, multicenter study to assess the efficacy and safety of the investigational drug Equecabtagene Autoleucel (IASO R&D code: CT103A, Innovent R&D code: IBI326), a fully human CAR-T cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM) who have received 3 or more lines of treatment.

As of December 31, 2022, with a median follow-up of 18.07 months, deep and sustained responses were observed in 103 evaluable patients. Among these patients, the overall response rate (ORR) was 96.1%, and the stringent complete response/complete response (sCR/CR) rate was 77.7%. Among subjects without prior CAR-T therapy, the ORR reached 98.9%, the sCR/CR rate reached 82.4%, and the 12-month progression-free survival (PFS) rate was 85.5%.

Minimal residual disease (MRD) negativity rate is 94.2% in the total evaluable patients, and all patients who achieved CR or above were MRD negative. The median time to achieve MRD negativity was 15 days, with 80.8% of patients remaining MRD negative at 12 months post infusion.

In addition, Equecabtagene Autoleucel could persist in the body for an extended period of time the median duration was 307.5 days. 12 months after infusion, 50% of patients had a vector copy number (VCN) above the lower limit of detection; and 24 months after infusion, VCN could still be detected in 40% of the patients.

Based on the descriptive analysis, patients receiving eque-cel achieved MRD negativity irrespective of cytogenetics status，extramedullary disease status，number of prior lines of therapy，and performance status. It suggests that eque-cel as immune cell therapy showed strong killing effect to myeloma cells without affecting by these factors.

In the FUMANBA-1 study, 90 RRMM patients without prior CAR-T therapy were evaluable for MRD test at 10-5. The results showed:

(1) An important prognostic factor for progression-free survival (PFS) in patients with RRMM treated with Equecabtagene Autoleucel is sustained MRD negativity: When comparing the PFS of patients in different MRD negative duration groups, those in the ≥ 6 months and ≥ 12 months group were significantly better than those in the < 6 months group. This was particularly true for those in the ≥ 12 months MRD negative duration group.

(2) There is a correlation between the persistence of CAR-T cells and sustainability of MRD negativity after infusion of Equecabtagene Autoleucel: Overall, there is a positive correlation between the two. This was particularly evident in subgroup analysis. The Triple-class exposure subgroup, the previous autologous transplantation treatment history subgroup, the high-risk cytogenetic abnormality subgroup, etc., showed a moderate to strong positive correlation between the persistence of CAR-T cells (VCN persistence) after infusion of Equecabtagene Autoleucel and the duration of MRD negativity. The correlation may become more significant in the future with longer term follow-up data, which could further reveal the positive correlation between long-term survival of CAR-T cells and long-term maintenance of MRD negativity.

"Studies have shown MRD is a biomarker that affects the long-term survival of RRMM patients. It’s necessary to maintain MRD negativity to improve the prognosis of RRMM patients and extend PFS. Equecabtagene Autoleucel has overcome two difficulties faced by traditional therapies in maintaining MRD negativity. First, it has increased the proportion of patients with MRD-negative persistence past 12 months from less than 10% to 80%. Second, only one-time infusion is needed to achieve sustainable MRD negativity. Traditional therapies require continuous medication to maintain MRD negativity, and once medication is stopped, patients face the risk of relapse. Patients who do not stop the medication will be facing the potential risk of inducing drug-resistant clones. Long-term medication and complex therapies increase direct treatment costs, seriously affect patients’ quality of life. The adverse effects caused by long term treatment also increase indirect costs to patients and their families. With its outstanding long-term persistence in the body, Equecabtagene Autoleucel can achieve lasting and deep remission in RRMM patients who have failed multiple lines of treatment. We expect that it will give more patients the hope of a cure," said principal investigators Professor Lu-gui Qiu, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and Professor Chunrui Li, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology.

On December 11, 2023 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, reported that it has triggered the second development milestone payment under its global licensing agreement with Bristol Myers Squibb for BMS-986442, an Fc-enhanced bispecific TIGIT antibody (Press release, Agenus, DEC 11, 2023, View Source [SID1234638470]). Agenus will receive a $25 million cash payment from Bristol Myers Squibb with the dosing of the first patient in the phase 2 dose expansion portion of the ongoing CA115-001 clinical trial of BMS-986442.

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BMS-986442 (also known as AGEN1777) is a dual TIGIT and CD96 antagonist with an enhanced Fc region to improve tumor-reactive T cell responses. Bristol Myers Squibb licensed BMS-986442 from Agenus in 2021. The phase 1 dose escalation study in solid tumors is complete and the phase 2 portion of the dose expansion combination study evaluating the combination of BMS-986442 with nivolumab +/- chemotherapy is ongoing.

"The start of the phase 2 portion of the dose expansion study marks an exciting milestone for this differentiated anti-TIGIT program and an important step in potentially delivering a meaningful new option for cancer patients," said Chief Executive Officer, Garo Armen, Ph.D. "Similar to our lead program botensilimab, we engineered this bispecific TIGIT antibody with an Fc-enhanced design, which we believe to be a pivotal feature for boosting clinical activity. We look forward to the future development of this program together with our partner Bristol Myers Squibb, as we remain committed to delivering innovation in cancer research."

The agreement also includes up to $1.32 billion in additional development, regulatory and commercial milestones plus tiered double-digit to mid-teens royalties. Bristol Myers Squibb is solely responsible for the development and any subsequent commercialization of BMS-986442 and its related products worldwide. Agenus retains options to conduct clinical studies under the development plan, to conduct combination studies with certain other Agenus pipeline assets, to co-fund global development for increased U.S. royalties, and to co-promote BMS-986442 in the U.S. upon commercialization.

On December 10, 2023 bluebird bio inc. (NASDAQ: BLUE) reported that data for gene therapy program in transfusion-dependent (TDT) beta-thalassemia were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (Press release, bluebird bio, DEC 10, 2023, View Source [SID1234638368]). Updated follow-up data showed sustained treatment effect, reduced iron management burden and improved quality of life measures in patients with beta-thalassemia who require regular red blood cell transfusions following treatment with betibeglogene autotemcel (beti-cel) (FDA approved and marketed in the U.S. as ZYNTEGLO).

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"Long-term results presented at ASH (Free ASH Whitepaper) 2023 showed durable transfusion independence and a continued positive safety profile in patients with beta-thalassemia treated with our beti-cel gene therapy through up to nine years of follow-up," said Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. "These data represent the longest follow-up with a gene therapy for patients with beta-thalassemia requiring regular transfusions and continue to show that beti-cel is a potentially curative therapy across ages and genotypes, through the achievement of durable transfusion independence and normal or near-normal hemoglobin levels."

As of January 30, 2023, 63 patients had received beti-cel across four clinical studies with a median follow-up of 5 years (60.1 months; range: 23.8-109.5). These include two Phase 3 studies (N=41) that led to the FDA approval of ZYNTEGLO in August 2022 as the first and only gene therapy for patients with beta-thalassemia who require regular red blood cell transfusions.

Sustained Efficacy and Safety Results, and Improved Quality of Life Measures in Adult and Pediatric Patients With Transfusion-Dependent β-Thalassemia Up to 9 Years Post Treatment With Betibeglogene Autotemcel (beti-cel) (poster #1102)

Among patients in the Phase 3 studies, 90.2% (37/41) achieved transfusion independence (TI). As of the data cutoff date, TI was maintained through last follow-up (up to 6 years) across ages and genotypes. Among patients in the Phase 1/2 studies, 68.2% (15/22) achieved TI, with 14 patients sustaining TI through the last follow-up (up to 9 years). One patient, with human immunodeficiency virus complicated by gastrointestinal infection and bleeding, no longer met protocol-defined TI as a result of a hemoglobin level <9 g/dL at year 6. The patient continued to benefit from beti-cell therapy and was not receiving chronic red blood cells transfusions as of the last follow-up.

Among 12 adult patients and 22 pediatric patients in the Phase 1/2 and Phase 3 studies, health-related quality of life (HRQOL) was assessed at baseline and every 6 months. Clinically meaningful improvements in quality of life assessments, including various quality of life assessments for mental, physical and psychosocial health, were demonstrated in both adult and pediatric patients up to 36 months.

As of the cutoff date, the safety results following beti-cel treatment largely reflected the known side effects of hematopoietic stem cell collection and the busulfan conditioning regimen. Overall, 19% of patients experienced ≥1 beti-cel-related AE. The most common beti-cel-related AEs (occurring in ≥3 patients) were abdominal pain (7.9% of patients) and thrombocytopenia (4.8% of patients). Five patients experienced serious veno-occlusive liver disease; all 5 received defibrotide and recovered. No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported.

Improvement in Iron Burden in Patients With Transfusion-Dependent β-Thalassemia (TDT) Treated With Betibeglogene Autotemcel (beti-cel) Gene Therapy: Up to 9 Years of Follow-Up (poster #2480)

Additionally, iron management outcomes were presented from patients with transfusion-dependent beta-thalassemia who completed either a Phase 1/2 or Phase 3 beti-cel parent study and subsequently enrolled in the long-term follow-up study and were followed for up to 9 years. Across all studies, 37/51 patients restarted chelation, and 12 received phlebotomy post-infusion; however, 69% (35/51) were able to stop chelation therapy, demonstrating restoration of iron levels over time and reduced iron management burden in those patients.

About ZYNTEGLO (betibeglogene autotemcel) or beti-cel

ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene therapy. It is approved for the treatment of beta-thalassemia in adult and pediatric patients who require regular red blood cell transfusions and was launched commercially more than a year ago. ZYNTEGLO works by adding functional copies of a modified form of the beta-globin gene (βA-T87Q-globin gene) into a beta-thalassemia patient’s own hematopoietic (blood) stem cells to enable the production of a modified functional adult hemoglobin (HbAT87Q). Once a patient has the βA-T87Q-globin gene, they have the potential to increase ZYNTEGLO-derived adult hemoglobin (HbAT87Q) and total hemoglobin to normal or near normal levels that can eliminate the need for regular red blood cell (RBC) transfusions.

Indication

ZYNTEGLO is indicated for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions.

Important Safety Information

Delayed Platelet Engraftment

Delayed platelet engraftment has been observed with ZYNTEGLO treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% of patients had ≥ Grade 3 decreased platelets on or after Day 100.

Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise.

Risk of Neutrophil Engraftment Failure

There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with ZYNTEGLO, provide rescue treatment with the back-up collection of CD34+ cells.

Risk of Insertional Oncogenesis

There is a potential risk of LVV mediated insertional oncogenesis after treatment with ZYNTEGLO.

Patients treated with ZYNTEGLO may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO, and integration site analysis at Months 6, 12, and as warranted.

In the event that a malignancy occurs, contact bluebird bio at 1 833-999-6378 for reporting and to obtain instructions on collection of samples for testing.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity reactions, including anaphylaxis.

Anti-retroviral and Hydroxyurea Use

Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed. If a patient requires anti-retrovirals for HIV prophylaxis, then confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.

Interference with Serology Testing

Patients who have received ZYNTEGLO are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV. Therefore, patients who have received ZYNTEGLO should not be screened for HIV infection using a PCR-based assay.

Adverse Reactions

The most common non-laboratory adverse reactions (≥20%) were mucositis, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (>50%) include neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia.

Drug Interactions

Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates.

Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate.

Pregnancy/Lactation

Advise patients of the risks associated with conditioning agents, including on pregnancy and fertility.

ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician.

ZYNTEGLO is not recommended for women who are breastfeeding, and breastfeeding after ZYNTEGLO infusion should be discussed with the treating physician.

Females and Males of Reproductive Potential

A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before ZYNTEGLO administration.

Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of ZYNTEGLO.

Advise patients of the option to cryopreserve semen or ova before treatment if appropriate.

Please see full Prescribing Information for ZYNTEGLO.

On December 10, 2023 Nona Biosciences, a global pioneer of technology innovation and antibody discovery and development solutions, and Evive Biotech, a global biopharmaceutical company devoted to developing a portfolio of novel biological therapies for patients worldwide, reported a collaboration agreement on antibody discovery based on the Harbour Mice antibody technology platform of Nona Biosciences (Press release, Nona Biosciences, DEC 10, 2023, View Source [SID1234638384]). The collaboration brings together professional advantages of Nona Biosciences and Evive Biotech, aiming to accelerate the process of antibody discovery and drug development to benefit patients faster.

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Harbour Mice is a proprietary antibody technology platform that utilizes the transgenic mouse to generate fully human monoclonal antibodies in both a traditional two heavy and two light chain (H2L2) format and a heavy chain only (HCAb) format. This platform holds significant potential for the development of therapeutic antibodies and the acceleration of drug discovery and development.

"Nona Biosciences is committed to bringing antibody discovery and research solutions to our partners better and faster," said Jingsong Wang, MD, PhD, Chairman of Nona Biosciences. "With the capabilities of Harbour Mice, we look forward to empowering our partners in antibody drug discovery and development, and helping more patients benefit from cutting-edge technologies and therapies."

"There is tremendous potential in antibody-based therapy, and I am very excited about this collaboration," said Simon Li, MD, PhD, CEO & CMO of Evive Biotech. "Evive Biotech’s mission is to develop innovative biologic therapies for patients worldwide. We eagerly anticipate collaborating with Nona Biosciences to accelerate the discovery of innovative antibody therapies to benefit patients across the globe."