On December 13, 2021 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, reported interim results from its Phase 1/2 PRIME clinical trial of P-BCMA-101 for the treatment of relapsed/refractory multiple myeloma (R/R MM) at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Poseida Therapeutics, DEC 13, 2021, View Source [SID1234596958]).

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The results show that P-BCMA-101, a non-viral transposon-based autologous CAR-T, was well tolerated and demonstrated strong anti-tumor activity in advanced, late line R/R MM patients. The learnings from P-BCMA-101 informed the development of the Company’s first allogeneic program, P-BCMA-ALLO1 which is also being evaluated in R/R MM patients. The Company previously announced that it is winding down the P-BCMA-101 autologous program in favor of the allogeneic program, P-BCMA-ALLO1.

"We are encouraged by the outcomes seen from our clinical trial of P-BCMA-101, results that continue to validate our approach and that have informed P-BCMA-ALLO1, our first fully allogeneic CAR-T program for patients with multiple myeloma, as well as our other programs. Our focus is on creating differentiated product candidates with a high percentage of T stem cell memory (Tscm) cells," said Eric Ostertag, M.D., Ph.D., chief executive officer of Poseida Therapeutics. "Looking ahead, we continue to advance P-BCMA-ALLO1 and P-MUC1C-ALLO1 and look forward to presenting data in 2022 for both of these allogeneic programs."

The PRIME trial is a Phase 1/2, open label 3+3 single dose escalation of P-BCMA-101 CAR-T cells. The primary objective of the study is to determine the safety and maximum tolerated dose of P-BCMA-101 based on dose limiting toxicities (DLT), and the key secondary objective is to assess the anti-myeloma effect of the product. The median patient age was 62, with a median time since diagnosis of approximately 5.8 years. Patients were heavily pre-treated, with a median of 7 prior lines of therapy (2-18). As of the data cut-off date of October 15, 2021, a total of 98 patients have been dosed with P-BCMA-101.

The best observed treatment regimen was a combination with rituximab (n=14), with an overall response rate (ORR) of 78%, a VGPR/sCR rate of 43% and 100% overall survival at the time of the data cutoff. Progression free survival was also improved with rituximab, with median overall survival rates not yet reached in several cohorts including the rituximab combination cohorts. Response rates for other cohorts are consistent with results previously reported.

Across the study, no dose-limiting toxicities were observed. 28% of patients developed cytokine release syndrome (CRS) and 7% of patients developed neurotoxicity. None of the patients developed Grade 3 or higher CRS, and 2% of patients developed Grade 3 neurotoxicity. There were no treatment-related deaths among the patient population and no patients needed ICU admission as a result of CAR-T related toxicities. 28 patients were treated on a fully outpatient basis.

"P-BCMA-101 demonstrated strong anti-tumor activity in advanced multiple myeloma patients, and cohorts to date have shown minimal CRS and neurotoxicity, which allows for safe administration in an outpatient environment and combinations with other therapies," said Caitlin Costello, M.D., Associate Clinical Professor of Medicine and member of the Division of Blood and Marrow Transplantation at the University of California, San Diego. "These data indicate that the piggyBac transposon-based platform is an attractive option for allogeneic CAR-T cells, which has led to a first-in-human Phase 1 study."

The Company’s first fully allogeneic CAR-T cell product, P-BCMA-ALLO1 utilizes Poseida’s proprietary piggyBac DNA delivery system and Cas-CLOVER site-specific gene editing system to create an allogeneic product that prevents both graft-vs-host and host-vs-graft diseases and also incorporates a next-generation BCMA binder. P-BCMA-ALLO1 manufacturing involves a proprietary "booster" molecule that allows for numerous doses to be produced from a single manufacturing run, while maintaining desirable Tscm cells, which can reach percentages in the 60-80% range.

The Investigational New Drug (IND) application for P-BCMA-ALLO1 was given a safe to proceed designation by the FDA in August 2021. The Phase 1 study is an open label, dose escalation study following a 3+3 design of dose escalation in subjects with R/R MM. The study will assess the safety and maximum tolerated dose of P-BCMA-ALLO1 based on dose limiting toxicities. Key secondary objectives of the study include the anti-myeloma effect and safety of P-BCMA-ALLO1.

On December 13, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs reported that positive data from the fully enrolled pivotal Phase 3 SIERRA trial of Iomab-B was presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH) (Free ASH Whitepaper) that is being held December 11 – 14, 2021 in Atlanta, Georgia and virtually (Press release, Actinium Pharmaceuticals, DEC 13, 2021, View Source [SID1234596955]). Iomab-B is an antibody radiation conjugate (ARC) targeting CD45 with the Iodine-131 radioisotope payload that is intended to be a targeted conditioning regimen to enable patients to access a bone marrow transplant (BMT). The pivotal Phase 3 SIERRA trial is the only randomized Phase 3 trial for patients age 55 and above with active, relapsed or refractory acute myeloid leukemia (r/r AML) where BMT, the only potentially curative treatment option for this patient population, is feasible. SIERRA is a randomized trial that will compare outcomes of patients receiving Iomab-B and a BMT to those of patients on the control arm receiving physician’s choice of salvage therapy including recently approved targeted agents venetoclax (Bcl-2), midostaurin and giltiritinib (FLT-3), and ivosidenib (IDH) who can potentially receive a BMT if they achieve a remission.

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BMT Engraftment Rates in Evaluable Patients Throughout the SIERRA Trial

BMT Engraftment

25% enrollment
(n=38)

50% enrollment
(n=76)

75% enrollment
(n=113)

100% enrollment
(n=151)

SIERRA

100%

100%

100%

100%*

Conventional
Care

21%

18%

17.5%

17%

Iomab-B
Crossover

100%

100%

100%

100%

• Does not include data from 6 Iomab-B patients for which BMT engraftment and 100-day non-relapse transplant mortality data is still maturing

Dr. Avinash Desai, Actinium’s Chief Medical Officer, said, "The remarkably consistent and high rates of BMT engraftment together with the low rates of non-relapse transplant related mortality at day 100 with Iomab-B through 100% enrollment give us great confidence in SIERRA. Despite 9 AML therapies approved since 2017, many of which are targeted, outcomes for relapsed or refractory patients remain dismal and potentially curative bone marrow transplant is rarely accessible, especially for older patients with active disease like those in SIERRA. This is supported by the fact that only 17% of patients were able to go to transplant in the control arm, which included many of the newly approved targeted therapies. We are highly encouraged that the separation in the number of patients potentially evaluable for the primary endpoint of six-month durable complete remission has remained at approximately 5-times or greater through all data analyses and now at full enrollment."

Grade > 3 Adverse Events

Adverse Event

Iomab-B (n=75)

N (%)

Control Arm (n=76)

N (%)

Sepsis p=0.002

4 (5.3%)

18 (23.7%)

Febrile neutropenia

25 (33.3%)

34 (44.7%)

SIERRA Patient Demographics Through 100% Enrollment

Patients in the Iomab-B arm were a median age of 64 (range: 55-77) and had a median blast count of 30% (range: 2-97) while patients in the control arm were a median age of 65.5 (range: 55-76) and had a median blast count of 20% (range: 3-97)
Over 60% of patients in SIERRA had adverse cytogenetics and over 32% had intermediate risk cytogenetics
Over 50% of patients were primary induction failures, approximately 25% had early relapse (less than 6 months) and the remaining patients were relapsed or refractory or second relapse
66% of patients enrolled in SIERRA received and failed targeted therapies with 66% of patients receiving venetoclax (Bcl-2) based treatment
47% of patients randomized to the control arm in SIERRA received targeted therapies with 81% of patients receiving Venetoclax-based treatment
Dr. Desai continued, "Given the advanced age, high-risk cytogenetic profile, poor disease status and florid active disease of the SIERRA patient population, it is remarkable that Iomab-B has enabled BMT engraftment in 100% of all evaluable patients receiving a therapeutic dose. We are also highly encouraged by the safety and tolerability profile of Iomab-B, which we believe is the result of its targeted nature. We have shown that Iomab-B can deliver high amounts of radiation to the bone marrow but spare vital organs such as the GI tract. We believe this has resulted in the significantly lower rate of sepsis in the Iomab-b arm compared to the control arm, which is a leading cause of transplant related mortality. In addition, lower rates of other adverse events – such as febrile neutropenia combined with the lower rates of 100-day non-relapse transplant related mortality – in the SIERRA arm is exciting. With the final Iomab-B patient receiving their BMT in November 2021, we can confirm our expectation for topline data in the third quarter of 2022. We look forward to presenting additional BMT engraftment, safety and 100-day non-relapse transplant related mortality data from the fully matured data set at a medical conference in early February."

Sandesh Seth, Actinium’s Chairman and CEO, added, "Data from the SIERRA trial have continuously validated our enthusiasm for Iomab-B and its potential to improve patient outcomes. We are struck by not only the consistency of the universal BMT engraftment rates at 25%, 50%, 75% and now 100% enrollment but also the consistency of the SIERRA data with the multiple studies conducted at the Fred Hutchinson Cancer Research Center, which drove our decision to license Iomab-B. As data from the SIERRA trial evolved, the vision to drive a paradigm shift in BMT conditioning, which currently relies on decades old, non-targeted chemotherapy-based regimens that limit access and hinder outcomes, by bringing Iomab-B forward as a targeted conditioning regimen became clear. It is an incredibly exciting time for Actinium to have completed SIERRA trial enrollment and to be on the cusp of producing data to support a BLA filing with the FDA and potential approval. If approved, we will be in a position to execute our vision of leading the paradigm shift to make targeted conditioning for BMT a reality."

The ASH (Free ASH Whitepaper) SIERRA presentation can be accessed on Actinium’s investor relations page View Source

About the SIERRA Phase 3 Trial

The SIERRA trial is a 150-patient, randomized clinical trial, studying Iomab-B compared to the control arm of physician’s choice of salvage therapy in patients with active, relapsed or refractory acute myeloid leukemia (r/r AML) age 55 and above. In SIERRA, patients receiving Iomab-B, those achieving a remission after salvage therapy or those patients not achieving remission after salvage therapy that crossed over to receive Iomab-B were offered a bone marrow transplant (BMT), which is the only treatment option with curative potential for patients with active r/r AML. The SIERRA trial is the only randomized Phase 3 trial intended to offer BMT to this patient population. The control arm of SIERRA included over 20 single agents or combination treatment options based on physician’s choice which include salvage chemotherapy and recently approved targeted agents including Bcl-2 inhibitor (Venetoclax), FLT3 inhibitors and IDH 1/2 inhibitors as there is no standard of care for this patient population. The SIERRA trial was conducted at 24 sites in the United States and Canada.

About Iomab-B

Iomab-B (I-131 apamistamab) via the monoclonal antibody apamistamab, targets CD45, an antigen widely expressed on leukemia and lymphoma cancer cells, immune cells and bone marrow stem cells. Apamistamab is linked to the radioisotope iodine-131 (I-131) and once attached to its target cells emits energy that travels about 100 cell lengths, destroying a patient’s cancer cells and ablating their bone marrow. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B may avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer (induction) and marrow cells (myeloablation) including those in bone marrow niches due to the "crossfire" effect enabled by the I-131 radioisotope.

Iomab-B was licensed from the Fred Hutchinson Cancer Research Center where it was studied in nearly 300 patients, in multiple clinical trials in 6 blood cancer indications. Iomab-B is being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are age 55 and above. The SIERRA trial was conducted at 24 preeminent transplant centers in the U.S. and Canada. The primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than the non-targeted intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Additional information on Iomab-B and the Phase 3 SIERRA clinical trial can be found at www.sierratrial.com.

On December 13, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that further progress on obecabtagene autoleucel (obe-cel) in an oral presentation [Abstract 477] entitled "Industrialization of an Academic Miltenyi Prodigy-Based CAR T Process" at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held between December 11-14, 2021 (Press release, Autolus, DEC 13, 2021, View Source [SID1234596952]). The Company also presented an update of obe-cel in relapsed/refractory aggressive and indolent B-Cell Non-Hodgkin’s Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL) patients from the ALLCAR19 extension study, as well as preclinical and initial engraftment data with AUTO1/22 in Pediatric ALL in two separate poster presentations [Abstracts 3823 and 1710, respectively].

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"We continue to observe sustained responses with obe-cel, with an EFS of 46% at 24 months and patients approaching up to 42 months of durability in the ALLCAR-19 study, supporting the curative potential of obe-cel as a standalone therapy in r/r B-ALL patients. Furthermore, we were encouraged to observe comparable safety and high complete response data between patients treated in the academic ALLCAR19 study and those in the Phase 1b portion of the Autolus sponsored FELIX study," said Dr. Christian Itin, chief executive officer of Autolus. "In addition, we are excited to observe further positive data for obe-cel in r/r B-NHL and B-CLL patients, as well as compelling initial data for AUTO1/22, pointing to the potential for indication expansion and life cycle management opportunities longer term."

Obe-cel in Adult Acute Lymphoblastic Leukemia patients (FELIX study)
Oral Presentation Title: Industrialization of an Academic Miltenyi Prodigy-Based CAR T process
Session Name: 711. Cell Collection and Processing: Advances in Mobilization, Collection, Manipulation and Engineering of HSCs and T Cells
Abstract: #477
Date: Sunday, December 12, 2021
Session Time: 12:00 PM – 1:30 PM ET; Presentation Time: 12:30 PM ET
Location: Georgia World Congress Center, Hall A1
Presenter: Dr. Claire Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

Initial experience in the phase 1b portion of the FELIX 1b/2 study (NCT04404660) resulted comparable results as seen in the Phase 1 ALLCAR19 study. As of the cut-off date of 13 September, 16 patients in the Phase 1b part of the FELIX study had received obe-cel. Patient characteristics in the FELIX 1b portion were broadly comparable to those observed in the ALLCAR19 study in r/r adult B-ALL.

As of the data cut off date of 15 October 2021, ALLCAR19 data shows morphological EFS for obe-cel is 46% at 24 months with a median follow-up of 29.3 months and patients approaching up to 42 months of durability.
Baseline characteristics between FELIX Phase 1b and ALLCAR19 studies are similar. 75% patients in the FELIX Phase 1b had >20% blasts at pre-conditioning, compared with 60% patients in ALLCAR19. 56.3% patients received prior blinatumomab in the FELIX Phase 1b study compared with 25% in ALLCAR191.
High level of CR/CRi response rate at 1 month observed across both studies, with 12/16 patients in the FELIX Phase 1b study, consistent with 17/201 patients in the ALLCAR19 study.
Safety consistent between the ALLCAR19 study and FELIX Phase 1b study, with no patient having high grade (≥Grade 3) cytokine release syndrome (CRS). 1 of 16 patients experienced a Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) in the FELIX Phase 1b study, as compared with 3 of 20 patients in ALLCAR-19 study1.
The company expects to present data from the Phase 2 portion of the FELIX study in 2022.

1 Roddie et al. "Durable responses and low toxicity after fast off-rate CD19 CAR-T therapy in adults with relapsed/ refractory B-ALL." DOI: 10.1200/JCO.21.00917 Journal of Clinical Oncology – published online before print August 31, 2021

Obe-cel (AUTO1) in Adult Acute Lymphoblastic Leukemia patients (ALLCAR study)
Poster Presentation Title: Safety and Efficacy of AUTO1, a Fast-Off Rate CD19 CAR in Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)
Session Title: 704. Cellular Immunotherapies: Clinical: Poster III
Abstract: #3823
Date: Monday, December 13, 2021
Presentation Time: 6:00 PM – 8:00 PM ET
Location: Georgia World Congress Center, Hall B5
Presenter: Dr. Claire Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

As of the data cut-off date of October 15, 2021, 15 r/r B-NHL and 1 B-CLL patient had received obe-cel with 14 patients evaluable for response.

14 of 14 patients responded to obe-cel of which 13 of 14 patients achieved complete metabolic response per Lugano 2014, with 1 B-CLL patient in PR.
15 of 16 patients were without disease progression at last follow-up, with 1 of 16 patients having died in CR from COVID-19. Furthermore, long term persistence was demonstrated by qPCR.
Median follow up time for Follicular Lymphoma (FL) and DLBCL patients was 11.8 months (range 2-14.2m).
Median follow up time for Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma patients was 7.4 months (range 1.1-14.8m).
Across all patients, obe-cel demonstrated a favorable safety profile with no ICANS or severe Grade ≥ 3 CRS events.
The company expects to present further data from more B-NHL and CLL patients in H1 2022.

AUTO1/22 in Pediatric Acute Lymphoblastic Leukemia patients (CARPALL)
Poster Presentation Title: A high sensitivity aCD22 CAR combined with aCD19 CAR to generate dual targeting CAR T cells for the treatment of r/r B-ALL
Session Title: 703. Cellular Immunotherapies: Basic and Translational: Poster I
Abstract: #1710
Date: Saturday, December 11, 2021
Presentation Time: 5:30 PM – 7:30 PM ET
Location: Georgia World Congress Center, Hall B5
Presenter: Dr. Sara Ghorashian, MD, PhD, Hon clinical senior lecturer, UCL Great Ormond Street Institute of Child Health

Obe-cel had previously been tested in r/r pediatric B-ALL2 in the CARPALL Study. Whilst obe-cel was safe and effective, similar to other studies in pediatric B-ALL, antigen escape was a common cause of treatment failure. AUTO1/22 has been designed to address antigen escape by the co-expression of a CD22 CAR with the CD19 CAR in obe-cel. Pre-clinical data demonstrated a high level of in vitro and in vivo activity of AUTO1/22 against leukemia cells. AUTO1/22 was shown to control leukemia in a mouse model of CD19 negative escape. AUTO1/22 is currently being tested in a study of r/r pediatric B-ALL. As of the cut-off date of October 21, 2021, 6 patients had received AUTO1/22. All patients showed engraftment of single and double CAR positive populations, pointing to early CAR T cell persistence. We expect to present clinical data from the full cohort of patients in H1 2022.

2 Ghorashian et al. "Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR." Nature Medicine volume 25, pages1408–1414(2019) (Sept 25, 2019)

Investor call details
Management will host a conference call and webcast on Monday, December 13, 2021 at 8:00 am ET/1:00 pm GMT to discuss the ASH (Free ASH Whitepaper) data. 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 9036269. 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 9036269.

On December 13, 2021 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, reported that its research collaborators at the Fred Hutchinson Cancer Research Center presented nonclinical data of STRO-002 and STRO-001 in two oral presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH 2021) in Atlanta, Georgia (Press release, Sutro Biopharma, DEC 13, 2021, View Source [SID1234596951]). The research was conducted by investigators from the laboratory of Soheil Meshinchi, M.D., Ph.D., Professor, Clinical Research Division at Fred Hutchinson Cancer Research Center and Professor, Division of Pediatric Hematology-Oncology at the University of Washington School of Medicine.

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Dr. Meshinchi commented, "Using a computational approach, we have identified FOLR1, or FolRα, as an actionable target for high-risk pediatric AML; and CD74 as an actionable target in adult and pediatric AML and ALL. We further demonstrated that STR0-002 effectively targets a high-risk AML subtype and STRO-001 effectively targets AML and ALL cells that express CD74, providing promising nonclinical data for possible treatment options."

Nonclinical data was presented by Quy Le, Ph.D., Staff Scientist, Meshinchi Lab, Fred Hutchinson Cancer Research Center on Sutro’s folate receptor alpha (FOLR1 or FolRα) -targeting antibody-drug conjugate (ADC), STRO-002, as a potential therapeutic in a rare pediatric acute myeloid leukemia (AML) subtype expressing FolRα. RNA-sequencing data demonstrated that FOLR1 is uniquely expressed in CBFA2T3-GLIS2 fusion (CBF/GLIS) AML and absent in other AML subtypes and normal hematopoietic cell populations. Data from an AML cell line engineered to express FOLR1 and CBF/GLIS-transduced cord blood hematopoietic stem/progenitor cells (CB HSPCs) demonstrated high cytotoxicity of STRO-002. In FOLR1 positive and CBF/GLIS-transduced CB HSPCs xenograft models, STRO-002 demonstrated potent activity that led to complete leukemia clearance.

Nonclinical data was also presented by Quy Le, Ph.D., Staff Scientist, Meshinchi Lab, Fred Hutchinson Cancer Research Center on Sutro’s CD74-targeting ADC, STRO-001, as a potential therapeutic in AML and acute lymphoblastic leukemia (ALL). Data from AML and ALL cell lines, as well as from nonclinical xenograft models, demonstrated robust in vitro and in vivo cytotoxicity of STRO-001 on cells expressing high- to -moderate levels of CD74, with no cytotoxicity observed in cells without CD74 expression. Potent anti-leukemia activity was also demonstrated in three primary AML patient samples with varied CD74 expression levels.

Dr. Arturo Molina, Sutro’s Chief Medical Officer added, "These nonclinical data presented by collaborators at Fred Hutchinson Cancer Research Center demonstrates the potential of targeted ADCs as therapeutics for AML and ALL. These data provide additional validation for an FolRα- and CD74-antigen directed approach, as our clinical studies for STRO-002 in ovarian and endometrial cancers and STRO-001 in B cell malignancies, respectively, continue to enroll patients."

On December 13, 2021 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company targeting virus-associated malignancies, reported that final data from its Phase 1b/2 trial of Nana-val in relapsed/refractory (R/R) EBV+ lymphoma (VT3996-201) were presented in an oral presentation at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Bradley Haverkos, M.D., Associate Professor at the University of Colorado School of Medicine (Press release, Viracta Therapeutics, DEC 13, 2021, View Source [SID1234596948]). Nana-val was well tolerated and continues to demonstrate promising activity with complete responses observed across multiple EBV+ lymphoma subtypes and a median duration of response of 10.4 months.

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Key data and conclusions from the ASH (Free ASH Whitepaper) presentation:

As of the October 28, 2021, data cutoff, 55 patients were enrolled. Patients had a median age of 60 (range 19-84) and had a median of two prior therapies. 75% (41/55) were refractory to their last therapy, and 96% (53/55) had exhausted all standard therapies (per Investigator).

Nana-val was generally well tolerated with reversible low-grade toxicities. The most commonly observed treatment emergent adverse events were reversible cytopenias, low grade creatinine elevations, and gastrointestinal symptoms.

Efficacy in evaluable patient (n=43):

Across all lymphoma subtypes: ORR = 40% (17/43); CR = 19% (8/43); Clinical Benefit Rate (CBR) [(CR+ partial response (PR) + stable disease (SD) ≥6 months] = 56% (24/43)
T/NK-NHL: ORR = 60% (9/15); CR = 27% (4/15); CBR = 67% (10/15)
Extranodal NK/T-Cell Lymphoma (ENKTL): ORR = 63% (5/8); CR = 13% (1/8); CBR = 63% (5/8)
Peripheral T-cell lymphoma (PTCL)/ Angioimmunoblastic T-cell lymphoma (AITL): ORR = 67% (4/6); CR = 50% (3/6); CBR = 83% (5/6)
DLBCL: ORR = 67% (4/6); CR = 33% (2/6); CBR = 83% (5/6)
Both DLBCL complete responses were in patients refractory to first line R-CHOP
IA-LPD: ORR = 50% (3/6); CR = 33% (2/6); CBR = 50% (3/6)
Durable responses:

Median DoR was 10.4 months
Three patients achieved responses with durations >2 years
"EBV is easily detectable and can be associated with a number of lymphoma subtypes, having a negative impact on clinical outcomes such as survival," said Dr. Haverkos, lead investigator of the VT3996-201 study. "The clinical safety and efficacy profile demonstrated thus far in this refractory patient population is very encouraging and underscores the utility of this unique EBV-targeted approach."

"Clinicians and key opinion leaders have shown a high level of enthusiasm for our potentially registration-enabling NAVAL-1 study, which we believe underscores the strength of the clinical dataset supporting the trial and the urgency of the unmet need in EBV-associated cancers. We expect this enthusiasm to be further bolstered following this oral presentation at ASH (Free ASH Whitepaper), which has provided us with the opportunity to broadly discuss the final Phase 1b/2 results with the clinical community," said Ivor Royston, M.D., President and Chief Executive Officer of Viracta. "We are encouraged by the final Phase 1b/2 data, as the response rates and median durations observed in the B- and T-cell lymphoma subtypes compare favorably to those seen in other single arm R/R lymphoma studies that have led to accelerated approvals and demonstrate Nana-val’s potential to provide meaningful clinical benefit to patients who currently lack effective treatment options. We look forward to the continued evaluation of this promising combination therapy in NAVAL-1 and anticipate providing further clinical program updates in 2022."

A copy of the ASH (Free ASH Whitepaper) presentation will be available by visiting the Events and Webcasts page of the Viracta website following the conference’s conclusion.

About Nana-Val (Nanatinostat and Valganciclovir)

Nanatinostat (VRx-3996) is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which is key to inducing viral genes that are epigenetically silenced in EBV-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-Val, in various subtypes of EBV-associated malignancies. Ongoing trials include a registration-enabling global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed/refractory EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 trial in patients with EBV+ recurrent or metastatic nasopharyngeal carcinoma and other EBV+ solid tumors.

About EBV-Associated Cancers

Approximately 95% of the world’s adult population is infected with Epstein-Barr virus (EBV). Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV+ lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden and is also associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.