On June 11, 2021 Imago BioSciences, Inc. ("Imago"), a clinical stage biopharmaceutical company discovering new medicines for the treatment of myeloproliferative neoplasms (MPNs), reported updates on two Phase 2 clinical trials of bomedemstat, one in patients with essential thrombocythemia (ET) and, the second in patients with advanced myelofibrosis (MF) (Press release, Imago BioSciences, JUN 11, 2021, View Source [SID1234583909]). The data were presented in two e-poster presentations during the 26th European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress (EHA 2021), taking place June 9-17, 2021.

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Poster title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) in Patients with Essential Thrombocythemia

The presented data show that bomedemstat was generally well-tolerated by patients with ET and demonstrated encouraging clinical activity as a monotherapy, showing symptomatic improvement in patients with significant MPN symptoms. Of the 12 patients dosed with bomedemstat for more than six weeks, 83% displayed substantial improvements in platelet count reduction, achieving platelets ≤ 400×109/L. Of the 10 patients entering the study with elevated white blood cell counts and evaluable at 12 weeks, 80% saw these counts fall within normal ranges. These improvements were achieved while maintaining stable hemoglobin levels. There were no dose limiting toxicities, no safety signals per Safety Advisory Board and one serious adverse event that was deemed unrelated.

"These encouraging data show that bomedemstat was well-tolerated and has the potential to bring meaningful clinical benefits for patients with essential thrombocythemia," said Wan-Jen Hong, M.D., chief medical officer of Imago BioSciences. "We are excited about these preliminary results from our lead asset, and look forward to completing enrollment of this study in order to lay the groundwork for a planned pivotal study in essential thrombocythemia."

Poster title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) in Patients with Advanced Myelofibrosis

The presented data from an ongoing Phase 2 study indicated that bomedemstat as a monotherapy for patients with advanced MF offered a distinct clinical benefit profile, and was generally well-tolerated among participants. Of the 16 patients evaluable at 24 weeks, 94% showed improvements in total symptom scores (TSS), with a reduction of 50% or greater in almost a third of this subset. In an analysis of 34 patients evaluated for mutant allele frequencies (MAFs), MAFs decreased in 44% of patients and were stable in 47%, with no new mutations in up to 660 days of follow-up. Of the 18 patients evaluable for splenomegaly at 24 weeks, 89% had a reduction in spleen volume, with that of one patient decreasing by more than 35%. There were no dose limiting toxicities, no safety signals per Safety Advisory Board, and no progression to acute myeloid leukemia (AML).

"These updated clinical results reveal that bomedemstat continues to offer distinct clinical benefits for patients with advanced MF, showing overall improvement in total symptom scores, spleen volumes and anemia," said Wan-Jen Hong, M.D., chief medical officer of Imago BioSciences. "The study is now fully enrolled, so we look forward to sharing our cumulative data as we continue to advance this investigational program for patients who have few therapeutic alternatives."

Poster presentations are available on the EHA (Free EHA Whitepaper) Virtual Congress platform. The posters will also be available on the Imago website here.

On June 11, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a poster presentation related to AUTO1 (obecabtagene autoleucel, obe-cel) in relapsed / refractory (r/r) indolent B cell lymphomas (IBCL) and included an update of duration of response in r/r adult Acute Lymphoblastic Leukemia (ALL) patients at the European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress 2021 (Press release, Autolus, JUN 11, 2021, View Source [SID1234583908]).

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"The stabilization of event-free survival at 50% between 12 months and 24 months of follow-up supports the curative potential of obe-cel as a standalone therapy for some adult ALL patients," said Dr. Christian Itin, chief executive officer of Autolus. "The early data we presented in indolent B cell non-Hodgkin lymphoma indicate a high level of clinical activity combined with a manageable safety profile and could represent a significant opportunity to expand the benefits of obe-cel treatment to a broader population of patients with B cell malignancies."

Title: Early safety and efficacy findings of AUTO1 (CAT19), a fast-off rate CD19 CAR, in Relapsed/Refractory Indolent B Cell Lymphomas

Presenter: Clare Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

Session Date and Time: Friday, June 11, 2021 at 9.00 a.m. CEST

Relapsed / refractory (r/r) indolent B cell lymphomas
As of the data cut-off date of May 17, 2021, 13 patients in Cohort D with r/r IBCL had been enrolled in the study and product was successfully manufactured for 12 patients, with one patient’s cells ongoing in manufacture. As of the data cut-off date, 9 r/r IBCL patients had received AUTO1 infusion. Three patients were pending infusion (including the patient noted above) and one patient died prior to lymphodepletion due to a Covid-19 infection. Obe-cel was well tolerated and demonstrated a favorable safety profile in adult patients with r/r low grade B-cell lymphoma, despite high disease burden. All treated patients achieved a complete metabolic remission and had robust CAR T engraftment, expansion, and persistence.

Grade 1 cytokine release syndrome (CRS) was reported in 4 patients and Grade 2 CRS in 1 patient. No immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade was observed in the study. At a median follow-up of 6 months (range 4.0-8.1m), eight of nine patients were disease free at last follow-up with one patient who relapsed at month 6 but was rescued with radiotherapy. One patient died of a COVID-19 infection at month 5.6 whilst in complete metabolic remission.

Relapse / refractory adult Acute Lymphoblastic Leukemia
As of the data cut-off date of May 17, 2021, 20 patients in Cohort A with r/r ALL had received obe-cel. The therapy was well tolerated, with no patients experiencing Grade 3 or higher CRS. Three patients (15%), all of whom had high leukemia burden (>50% blasts), experienced Grade 3 ICANS that resolved swiftly with steroids.

Of the 20 patients evaluable for efficacy, 17 (85%) of patients achieved minimum residual disease (MRD)-negative complete remission (CR) at one month. Most notably, the durability of remissions is highly encouraging. Across all treated patients, event free survival (EFS) at twelve months and twenty-four months is 50.2% with median EFS not being reached.

Conference Call
Management will host a conference call and webcast today at 8:30 am ET/1:30 pm BST to discuss the data presented at EHA (Free EHA Whitepaper). To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus’ website.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 3697562. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 3697562.

On June 11, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported updated interim data from the ongoing Phase 1/2 clinical trial investigating the safety and efficacy of MB-106 CD20-targeted, autologous CAR T cell therapy for high-risk B-cell non-Hodgkin lymphomas ("B-NHL") and chronic lymphocytic leukemia ("CLL") (Press release, Mustang Bio, JUN 11, 2021, View Source [SID1234583907]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Research Center ("Fred Hutch").

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The data presented in an e-poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress ("EHA2021") by Mazyar Shadman, M.D., M.P.H., Associate Professor, Clinical Research Division of Fred Hutch, included safety and efficacy data from the cell manufacturing process that was modified to combine the culture of CD4+ and CD8+ cells. In the 15 patients treated, the overall response rate ("ORR") was 93% (14/15) with a complete response ("CR") rate of 67% (10/15). In 11 patients with follicular lymphoma ("FL"), ORR and CR were 91% (10/11) and 82% (9/11), respectively. As of the time of the e-poster submission to EHA (Free EHA Whitepaper)2021, all patients who achieved CR remained in remission. One patient with FL had an initial partial response with a later disease progression, had a spontaneous CR and remains in remission. The patient with CLL also had a CR and undetectable measurable residual disease in peripheral blood and bone marrow by flow cytometry (10-4) (uMRD4) on day 28. CAR T persistence was seen in all dose levels ("DL") and, while expansion was faster in higher DL, the levels were comparable by day 28.

From a safety profile perspective, cytokine release syndrome ("CRS") occurred in 6 patients (40%): 3 patients with grade 1 and 3 patients with grade 2. Only 1 patient (6.5%) experienced grade 2 immune effector cell-associated neurotoxicity syndrome ("ICANS") and none of the 11 patients with FL experienced ICANS of any grade. No grade 3 or higher CRS or ICANS were seen in any patient.

Dr. Shadman commented, "MB-106 continues to demonstrate a very favorable safety and efficacy profile, as well as sustained complete responses. This compelling clinical activity, including the complete remissions in 67% of the patients in the trial, demonstrates the potential of MB-106 as a viable CD20-targeted CAR T cell therapy. We are pleased that all complete responders continue to remain in remission, and we continue to enroll all eligible CD20+ NHL and CLL patients into this trial."

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are encouraged by the updated MB-106 safety and efficacy data presented by Dr. Shadman today. As reported last month, the FDA has accepted Mustang’s IND application to initiate a multicenter Phase 1/2 clinical trial investigating the safety, tolerability and efficacy of MB-106 for relapsed or refractory B-NHL and CLL. We look forward to commencing the trial later this year and further advancing MB-106 for patients with B-NHL and CLL who are in need of new treatment options."

For more information on the clinical trial at Fred Hutch, please visit www.clinicaltrials.gov using the identifier NCT03277729.

Webinar
On Tuesday, June 15, 2021, at 1 p.m. ET, Mustang will host a webinar with Dr. Shadman and colleague Brian Till, M.D., both of Fred Hutch, to discuss the updated interim results from the ongoing Phase 1/2 clinical trial investigating the safety and efficacy of MB-106 CD20-targeted CAR T for B-NHL and CLL. Mustang’s management team will also provide more details on the planned MB-106 Phase 1/2 clinical trial to be conducted under Mustang’s Investigational New Drug ("IND") application. The Company recently announced that the U.S. Food and Drug Administration ("FDA") accepted its IND to initiate a multicenter Phase 1/2 clinical trial investigating the safety, tolerability and efficacy of MB-106 for relapsed or refractory B-NHL and CLL. Following the formal presentations, the Mustang team, along with Drs. Till and Shadman, will be available for questions. To register for the webinar, please click here. An archived replay will be accessible on the Events page of the Investor Relations section of Mustang’s website: www.mustangbio.com for approximately 30 days following the call.

About MB-106 (CD20-targeted CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division, and exclusively licensed to Mustang in 2017. MB-106 has been optimized as a third-generation CAR derived from a fully human antibody and is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHL and CLL. Additional information on the trial can be found at View Source using the identifier NCT03277729.

On June 11, 2021 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel therapies targeting diseases resulting from dysfunction of the CXCR4 pathway, reported positive preliminary efficacy and safety data from its ongoing Phase 1b clinical trial of its lead candidate mavorixafor, in combination with ibrutinib, in Waldenström’s macroglobulinemia patients with both MYD88 and CXCR4 mutations (Press release, X4 Pharmaceuticals, JUN 11, 2021, View Source [SID1234583905]). These data are included in a poster published today at this year’s European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress.

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"We are very pleased to present this exciting first look at the data from our ongoing Phase 1b trial in double-mutation Waldenström’s patients," said Diego Cadavid, M.D., Chief Medical Officer of X4 Pharmaceuticals. "Despite still being in the low- and mid-dose ranges of mavorixafor, we are already seeing robust decreases in IgM levels – an important signal of clinical response – showing the potential benefit for mavorixafor in combination with ibrutinib. The combination therapy is demonstrating good tolerability and promising results across additional pharmacodynamic parameters, including increases in total hemoglobin and mobilization of white blood cells. We look forward to presenting longer-term data and an expanded data set from this trial later in the year."

"While ibrutinib has significantly advanced the treatment of Waldenström’s macroglobulinemia, we have observed that there remains a clinical unmet need for patients with concurrent CXCR4 and MYD88 mutations," said Steven Treon, M.D., Ph.D., FACP, FRCP, Director of the Bing Center for Waldenström’s Macroglobulinemia at Dana-Farber Cancer Institute, Professor of Medicine at Harvard Medical School, and the poster’s lead author. "I am encouraged by the preliminary safety and efficacy data from the ongoing combination trial of ibrutinib and mavorixafor in this difficult-to-treat patient population and look forward to continuing this important research."

Key Highlights of the Preliminary Low- and Mid-Dose Phase 1b Results

As of April 15, 2021, 8 patients had been enrolled in the Phase 1b clinical trial with a median duration of treatment of 156 days; data presented are primarily from patients in Cohort A who received low- and mid-range doses of mavorixafor plus ibrutinib; 4 patients were treated for more than six 28-day cycles.
Mavorixafor exposures tracked with sustained and dose-dependent increases in white blood cell counts, confirming target engagement and mavorixafor mechanism of action.
All patients (100%) experienced reductions in serum IgM and no patients’ disease progressed while on treatment.
At 6 months, mavorixafor plus ibrutinib showed signs of meaningful reductions in IgM versus comparable, previously published data of ibrutinib monotherapy in double-mutation patients:
Patients achieved median reductions of 60%-75% in serum IgM levels normalized to baseline; this compares to published ibrutinib monotherapy reductions of 38%-45% in double-mutation patients.
2 out of 4 patients (50%) had >50% reduction in serum IgM from baseline; comparable reductions have been reported in only 28%-38% of double-mutation patients on ibrutinib monotherapy.
One patient achieved IgM levels within normal range, a key criterion for a complete response.
All patients with hemoglobin levels below normal at baseline had increases during treatment, with a median change in hemoglobin of >20 g/L, approaching normal levels and suggesting reduction in cancer burden in the bone marrow.
Mavorixafor and ibrutinib exposures were consistent with previous single-agent studies, suggesting no drug-drug interactions.
Data suggest that mavorixafor plus ibrutinib is well tolerated with no serious adverse events reported.
Patient enrollment and dose escalation to the highest mavorixafor dose (600 mg) continues.
The e-poster (EP784) entitled: "Preliminary Clinical Data From a Phase 1b Study of Mavorixafor and Ibrutinib in Patients With Waldenström’s Macroglobulinemia With MYD88 and CXCR4 Mutations" is now available on the X4 corporate website. Conference attendees can access an accompanying audio presentation by Dr. Treon on the Congress website.

X4 will host a conference call and webcast at 7:00 am ET today that will include presentations by X4 senior executives and a "Fireside Chat" and Q&A with poster co-author Christian Buske, M.D., Director of the Institute of Experimental Cancer Research and Attending Physician, Senior Consultant at the University Hospital of Ulm, and Founder and Coordinator of the European Consortium for Waldenström’s Macroglobulinemia.

The conference call can be accessed by dialing (866) 721-7655 (domestic) or (409) 216-0009 (international), followed by the conference ID: 4492859. The live webcast will be accessible on the Events & Presentations page of the company’s website at investors.x4pharma.com. The conference call slide deck will be made available upon completion of the event and the webcast replay will be available approximately two hours after the completion of the event on X4’s website.

This Phase 1b clinical trial is being conducted with the support of AbbVie Inc. and The Leukemia & Lymphoma Society’s Therapy Acceleration Program (LLS TAP).

About Waldenström’s Macroglobulinemia and Associated CXCR4 Mutations
Waldenström’s macroglobulinemia is a rare B-cell lymphoproliferative disorder characterized by increased immunoglobulin M (IgM). Greater than 90% of patients with Waldenström’s have acquired mutations in the MYD88 gene, with a subset (30%–40%) also having mutations in chemokine receptor CXCR4. The presence of the CXCR4 mutation is associated with greater cancer burden, higher serum IgM levels, and increased risk of developing a serious emergent condition called symptomatic hyperviscosity syndrome. Importantly, the presence of CXCR4 mutations has been shown to negatively impact patients’ response to ibrutinib (a BTK inhibitor), as manifested by delayed response, inferior depth of response, and/or shorter progression-free survival.

About Mavorixafor and the Phase1b Clinical Trial in Waldenström’s Macroglobulinemia
Mavorixafor is an oral small-molecule antagonist of the CXCR4 receptor with a demonstrated ability to inhibit binding of its ligand, CXCL12; this inhibition of CXCR4 has been shown to sensitize Waldenström’s cells with both MYD88 and CXCR4 mutations to BTK antagonists, such as ibrutinib. The ongoing Phase 1b, open-label, multicenter, single-arm study (NCT04274738) examines intra-patient dose escalation, safety, pharmacokinetics, and pharmacodynamics of mavorixafor in combination with ibrutinib in patients with a diagnosis of Waldenström’s macroglobulinemia and confirmed MYD88 and CXCR4 genetic mutations. In the study, patients are initiated on oral, once-daily doses of ibrutinib 420 mg and mavorixafor 200 mg (low dose); in Cohort A, patients are escalated to 400 mg mavorixafor (mid-dose) after 28 days if fewer than two dose-limiting toxicities are observed at the low dose; in Cohort B, patients are escalated from 200 mg to 400 mg and finally to 600 mg (high dose) after each dose level is deemed tolerable. Patients are followed for adverse events and change from baseline in serum IgM and hemoglobin, pharmacokinetics, and pharmacodynamic markers, including peripheral white blood cell counts (WBCs).

On June 11, 2021 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of innovative Anti-Cancer Therapy ("ACT") technologies intended to safely and effectively destroy various cancers, bacteria and viruses, while preserving patient Quality Of Life ("QOL") reported the launch of the seventh US-based Clinical Study Site ("CSS"); specifically, the University of Chicago Medicine ("UChicago Medicine") (Press release, Theralase, JUN 11, 2021, View Source [SID1234583904]). UChicago Medicine has successfully received Institutional Review Board ("IRB") approval allowing them to commence enrollment and treatment of patients in Theralase’s pivotal Phase II Non-Muscle Invasive Bladder Cancer ("NMIBC") Clinical Study ("Study II").

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Study II is focused on the enrollment and treatment of approximately 100 to 125 patients, who have been previously diagnosed with Bacillus Calmette Guérin ("BCG")-Unresponsive Carcinoma In-Situ ("CIS") or who are intolerant to BCG therapy ("Study II").

The Company has successfully launched five CSSs in Canada and 7 in the US for patient enrollment and treatment in Study II.

UChicago Medicine, with a history dating to 1927, is a not-for-profit academic medical health system based on the campus of the University of Chicago in Hyde Park, with hospitals, outpatient clinics and physician practices located throughout Chicago and its suburbs. UChicago Medicine translates fundamental scientific discoveries into better care for their patients and performs more clinical trials than any other hospital in Illinois.

Dr. Piyush Agarwal, MD, Professor of Surgery and Urology, Director, Bladder Cancer Program, Fellowship Director, Urologic Oncology, at UChicago Medicine stated, "This technology harnesses the power of near infrared light produced by a laser to destroy localized bladder cancer cells that have not responded to standard of care therapy such as BCG. It gives patients an option to consider before bladder removal."

Dr. Agarwal’s clinical and laboratory research focuses primarily on bladder cancer, specifically BCG-Unresponsive disease, the urinary microbiome, molecular targeted therapy and immunotherapy. He has conducted several original, investigator-initiated clinical studies and has presented his research at national and international meetings. Dr. Agarwal has served on the Food and Drug Administrations ("FDA") oncologic drug advisory committee and has authored six book chapters and over 90 manuscripts.

The first US-based patient in Study II was recently treated at Virginia Urology ("VU") ( Richmond, Virginia).

VU has a long history of providing quality care to the Greater Richmond metro area for over 75 years. VU prides itself on its strong commitment to the community’s urological needs by recruiting highly skilled physicians and using the latest technology. VU is comprised of over 40 physicians that include urologists and urogynecologists as well as physicians specializing in the urologic aspect of anesthesiology, pathology, radiation oncology, and radiology. Because VU has such diverse medical professionals, they are able to provide the latest technologies with their mission of providing the best possible care for each patient.

To date, Study II has enrolled and provided the primary study treatment for 20 patients (including three patients from Phase Ib study treated at the Therapeutic Dose) for a total of 23 patients.

Shawn Shirazi, PhD, Chief Executive Officer of Theralase, stated, "It is exciting to see Theralase clear another hurdle by treating the first patient in the US and move one step closer to achieving its next milestone of enrolling and treating twenty-five patients in early 2021. Once completed, Theralase plans to submit the clinical assessment data on the first twenty-five patients treated in Study II to the FDA for consideration of Break Through Designation ("BTD") status."