On June 10, 2022 Affimed N.V. (Nasdaq: AFMD) ("Affimed" or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported a poster at the Annual Meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) in Vienna, Austria (Press release, Affimed, JUN 10, 2022, View Source [SID1234615886]). The data demonstrate the cytotoxic potential of the CD123/CD16A-targeting bispecific innate cell engager (ICE) AFM28 which is in development as a novel treatment for patients with myeloid diseases, e. g. relapsed/refractory (R/R) acute myeloid leukemia (AML). AFM28 binds to natural killer (NK) cells and CD123-positive tumor cells and demonstrated the induction of tumor cell killing in vitro and a good tolerability and strong anti-tumor activity in vivo.

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"It is widely acknowledged that targeting CD123 holds significant untapped promise in developing better AML therapies. We believe our differentiated approach in targeting CD123 has the potential to provide a novel, innate immune system-engaging therapy to improve clinical outcomes," said Dr. Arndt Schottelius, Chief Scientific Officer at Affimed. "Following these encouraging pre-clinical proof-of-concept data and the experience we have gained from our AFM13 studies so far, we will be launching a first-in-human clinical study to investigate the compound’s safety, efficacy and biological activity as monotherapy later this year and in combination with adoptive NK cells soon after." The data presented at EHA (Free EHA Whitepaper) today provide validation of the mechanism of action (MoA) as well as preclinical proof-of-concept for AFM28 in a range of in vitro and in vivo assays. AFM28 exhibited high-affinity binding to CD16A expressed on NK cells and high avidity conferring long cell surface retention in comparison to Fc-enhanced anti-CD123 antibody. Moreover, AFM28 demonstrated the ability to destroy CD123-positive tumor cell lines and primary leukemic cells via antibody-dependent cell-mediated cytotoxicity (ADCC).

Importantly, AFM28 was active irrespective of mutational status of tumor cells and also induced depletion when CD123 expression was very low. Strikingly, AFM28 was also active against cells not killed by an Fc-enhanced CD123-targeting comparator antibody suggesting the potential for improved clinical effectiveness. Moreover, AFM28 also depleted leukemic cells from patient bone marrow without destroying CD34-positive/CD123-negative cells, suggesting sparing of hematopoietic stem and progenitor cells.

In vivo studies in an AML murine model demonstrated anti-tumor efficacy, and cynomolgus toxicology models predicted pharmacodynamic activity with a well-tolerated safety profile and low risk of cytokine release syndrome.

Efficient depletion of leukemic blasts and leukemic stem cells is critical for inducing long-term remission in AML patients. As both cell types express CD123, AFM28’s ability to redirect NK cells to this target killing both leukemic blasts and leukemic stem cells makes this an attractive treatment strategy. Currently, there are no curative immunotherapies available, the only option is allogenic hematopoietic stem cell transplantation (allo-HSCT). Affimed plans to initiate clinical development of AFM28 with a first-in-human phase 1 monotherapy trial in adult patients with R/R AML in the second half of 2022. In addition, Affimed plans to investigate AFM28 in combination with allogeneic NK cell therapy after a safe starting dose has been determined.

The full poster is accessible through the following link: Publications and Posters – Affimed

Poster details:
Title: Novel bispecific innate cell engager AFM28 for the treatment of CD123-positive acute myeloid leukemia and myelodysplastic syndrome
Authors: Jana-Julia Siegler, Nanni Schmitt, Jens Pahl, Torsten Haneke, Izabela Kozlowska, Séverine Sarlang, Alexandra Beck, Stefan Knackmuss, Paulien Ravenstijn, Uwe Reusch, José Medina-Echeverz, Jan Endell, Thorsten Ross, Daniel Nowak, and Christian Merz
Final abstract code: P482
Session date and time: Poster session on Friday, June 10th, 10:30 – 11:45 a.m. EDT / 16:30 – 17:45 CEST

About AFM28
AFM28, a tetravalent, bispecific CD123- and CD16A-binding ICE developed on Affimed’s ROCK platform, is designed to bring a new immunotherapeutic treatment to patients with CD123+ myeloid malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). It engages NK cells to initiate tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC), even at low CD123 expression levels. Clinical development is planned as both monotherapy and in combination with allogeneic NK cells in patients with relapsed/refractory CD123-positive leukemias.

On June 10, 2022 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radio pharmaceuticals as precision medicines, and Niowave, Inc., a manufacturer of medical radioisotopes from radium and uranium, reported that the companies have entered into a collaboration and supply agreement for the development, production, and supply of actinium-225 (Press release, Fusion Pharmaceuticals, JUN 10, 2022, View Source [SID1234615885]). Under the agreement, Fusion will invest up to $5 million in Niowave to further develop their technology to increase current production capacity of actinium-225, and in return Fusion will have guaranteed access to a pre-determined percentage of Niowave’s capacity of the resulting actinium-225, as well as preferred access to any excess supply produced. As part of the agreement, Fusion will also have an option to invest in future production of actinium-225 to scale with Fusion’s needs.

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"As excitement for the tumor-killing potential of alpha-emitting radio pharmaceuticals increases, we intend to stay at the forefront of actinium development and supply to support our growing pipeline of targeted alpha therapies," said Fusion Chief Executive Officer John Valliant, Ph.D. "We continue to prioritize manufacturing and access to actinium as a critical component of Fusion’s platform, and our partnership with Niowave further strengthens and diversifies our supply chain as we advance multiple actinium-based radio pharmaceuticals in the clinic."

"The Niowave team has worked hard to scale up our actinium-225 production to the millicurie level and this has allowed us to start working with oncology community partners," said Niowave Chief Executive Officer/Senior Scientist Terry Grimm, Ph.D. "We have been watching Fusion’s progress in the development of their pipeline of targeted alpha therapies and we are very excited to partner with them on this journey."

Fusion is developing actinium-based TATs leveraging the potency and precision offered by alpha particles. Actinium-225 decay gives off four alpha emissions in relatively rapid succession, maximizing the damage to the DNA of tumor cells, with a 10-day half life that allows for central manufacturing and distribution of products to clinical sites in a ready-to-use form.

Fusion currently has existing actinium supply arrangements with TRIUMF and the U.S. Department of Energy (DOE).

On June 10, 2022 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the publication of clinical data across multiple programs at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress, being held June 9-12, 2022 (Press release, Autolus, JUN 10, 2022, View Source [SID1234615884]).

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Autolus will hold a conference call on Monday June 13 2022 at 7:30 am EST / 12:30 pm BST, which will include participation from; Dr. Steven Horwitz, M.D., Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center; Dr. Kate Cwynarski, Chair UK T cell Lymphoma Group, Consultant Hematologist, University College London Hospital; and Autolus’ management team.

"We are excited to be presenting this first clinical data for two new product candidates, AUTO4 with its unique targeting approach for T cell lymphoma and AUTO1/22 a dual targeting CAR T product for the treatment of children with ALL," said Dr. Christian Itin, CEO of Autolus. "With obe-cel progressing towards pivotal data in the FELIX trial in adult patients with ALL, we are pleased to show obe-cel’s broader utility in B-NHL patients, mirroring the high level of activity and well manageable safety profile we have seen in previous trials."

"This year’s EHA (Free EHA Whitepaper) is an important meeting for Autolus with four presentations providing updates from ongoing clinical studies," said Dr. Martin Pule, Chief Scientific Officer of Autolus. "In an oral presentation we will present AUTO4 clinical data for the first time. These data suggest that AUTO4 has the potential to become an important therapeutic option for patients with T cell lymphoma. In a second presentation, we will present our finding from clinical testing of AUTO1/22. These data show that AUTO1/22 can induce remission in children with B-ALL, including in those whose disease was not successfully treated with commercial CAR T product. Further, data suggest that AUTO1/22 can prevent antigen escape. In two additional presentations, we demonstrate incremental obe-cel data in B-NHL and B-CLL, as well as some early data in PCNSL. Obe-cel continues to have consistent safety and efficacy data across these indications."

"As clinicians, we are always searching for new strategies to address unmet needs in aggressive blood cancers," said Dr. Steven Horwitz, M.D., Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York. "T Cell Lymphomas are particularly challenging, and I’ve been following Dr. Pule’s strategy of CAR T targeting based on the mutually exclusive expressions of TRBC1 or TRBC2 with great interest. Any advance in bringing new effective therapies to patients with T cell lymphomas is of great importance."

Data presentations:

Title: Safety and preliminary efficacy findings of AUTO4, a TRBC1-targetting CAR, in relapsed/refractory TRBC1 positive selected T Cell Non-Hodgkin Lymphoma
Session Title: Gene therapy and cellular immunotherapy – Clinical 2
Session date and time: Saturday, June 11, 2022 16:30 – 17:45 CEST
Session room: Hall Strauss 1-2
Final Abstract Code: S261
Presenting Author: Kate Cwynarski
Conclusions: As of April 26 2022, 10 patients with TRBC1-positive r/r T-cell lymphoma (Peripheral T-cell lymphoma Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell lymphoma (AITL), Anaplastic Large cell lymphoma (ALCL)) have been treated with AUTO4 in a Phase I dose escalation trial. Three patients had prior stem cell transplantation. After lymphodepletion with Flu/Cy, patients received either 25, 75, 225 or 450 x 106 CAR T cells. AUTO4 demonstrated a tolerable safety profile, with no patient experiencing any dose limiting toxicities, and no neurotoxicity/immune effector cell-associated neurotoxicity (ICANS) and no Grade 3 or higher infections. CRS was only seen at the highest dose level of 450 x 106 CAR T cells (Grade 3 in 1 patient; Grade 1-2 in 3 patients). As of 26 April 2022, 9 patients were evaluable for efficacy. At the highest dose level 3 of the 3 patients dosed achieved a complete metabolic remission (CMR) at 1 month. 2 of these patients remain in ongoing CMR by PET-CT at Month 3 and 6 respectively, whilst the 3rd relapsed at 3 months.
Title:Dual antigen targeting with co-transduced CD19/22 CAR T cells for relapsed/refractory ALL (AUTO1/22)
Session Title: Gene therapy and cellular immunotherapy – Clinical 1
Session date and time: Saturday, June 11, 2022 11:30 – 12:45 CEST
Session room: Hall Strauss 1-2
Final Abstract Code: S259
Presenting Author: Sara Ghorashian
Conclusions: As of May 27 2022, in 11 treated patients, we have reproducibly generated a product that is balanced in CD19 and CD22 CAR expression, with predominance of dual CAR T cells and having a mostly central memory phenotype. To date and in Kymriah-ineligible patients, AUTO1/22 has demonstrated a favorable safety profile. There have been no incidences of severe CRS, and one Grade 4 ICANS which was indistinguishable from chemotherapy-related leukoencephalopathy. We have seen excellent CAR T expansion, with only 4 patients losing CAR T persistence at the last follow up. Overall, 9 out of 11 patients achieved complete response, and there were 2 non-responders. Notably, 2 out of 3 patients with CD19-ve disease achieved complete response demonstrating the efficacy of the CD22 CAR. Two patients relapsed with CD19+CD22+ disease, a further patient had emergence of molecular MRD and all these events were associated with lack of CAR T Cell persistence. No antigen negative relapses were seen in responding patients. At a median follow up of 8.7 months, 6 of 9 responding patients were in MRD-negative complete remission (1-12 months) and the median duration of b-cell aplasia has not been reached.
Title: Safety and efficacy findings of AUTO1, a fast off-rate CD19 CAR, in relapsed/refractory Primary CNS Lymphoma
Session Title: Poster session
Session date and time: Friday, June 10, 2022 – 16:30 – 17:45 CEST
Final Abstract Code: P1460
Presenting Author: Claire Roddie
Conclusions: Excellent AUTO1 expansion was observed in the peripheral blood by qPCR, with persistence in all treated patients at last follow-up. No grade >/=3 CRS was observed using IV or I-VEN AUTO1 administration. Two cases of grade 3 ICANS were reported following IV infusion. In the first case the patient had several neurological deficits that evolved despite ICANS treatment and were compatible with progressive PCNSL, as confirmed with the month 1 MRI scan. The second case was a patient whose neurological deficits improved with steroids/anakinra. Encouraging response rates were observed: of 6 patients evaluable for efficacy following IV AUTO1, the ORR was 4/6 (67%), with 2 CRs and 2 PRs. These four responding patients are without disease progression at last follow up. Two patients died from progressive PCNSL on study. Longer follow-up is needed and enrolment of additional patients is ongoing.
Title: Safety and efficacy findings of AUTO1, a fast off-rate CD19 CAR, in relapsed/refractory B-Cell Non-Hodgkin’s Lymphoma (B-NHL), and chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
Session Title: Poster session
Session date and time: Friday, June 10, 2022 – 16:30 – 17:45 CEST
Final Abstract Code: P1459
Presenting Author: Claire Roddie
Conclusions: AUTO1 continues to display a favorable safety profile with no ICANS or Grade ≥ 3 CRS. Long term persistence of AUTO1 in the peripheral blood was demonstrated by qPCR. Of the 20 patients evaluable for efficacy, the overall response rate was 18/20 (90%). In the B-NHL cohorts the CRR was 16/17 (94%) (FL: 7/7, MCL: 3/3, DBCL: 6/7). In the CLL cohort a best response of a PR was achieved in 2/3 patients, notably both achieved MRD-negativity in their marrow and both remain in PR at 10 and 6 months respectively. Of the responding MCL, DLBCL, FL and CLL patients, 17/18 (94%) are without disease progression at last follow-up. One MCL patient relapsed six months following treatment and 1 FL patient died in CR from COVID-19. Longer follow-up and enrolment of additional MCL, FL, DLBCL and CLL patients is ongoing.
Conference Call
Management will host a conference call and webcast on June 13, 2022 at 7:30 am ET/12:30 pm BST to discuss the EHA (Free EHA 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: 6594553. 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: 6594553.

On June 10, 2022 Wugen, Inc., a clinical-stage biotechnology company developing a pipeline of off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, reported that new preclinical data demonstrating the enhanced anti-tumor properties of WU-NK-101, Wugen’s lead memory natural killer (NK) cell therapy product (Press release, Wugen, JUN 10, 2022, View Source [SID1234615883]). The data elucidate the unique cytokine-induced memory-like (CIML) phenotype of WU-NK-101 and further support its clinical development for acute myeloid leukemia (AML) and a range of solid tumor indications. The findings will be presented during a poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress in Vienna.

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"These data are foundational to our approach and confirm our development strategy as we advance WU-NK-101 for both AML and solid tumors," said Dan Kemp, Ph.D., President and Chief Executive Officer of Wugen. "Today’s presentation highlights key functional features of WU-NK-101: its unique CIML phenotype, enhanced metabolic fitness, and persistent cytotoxic activity, which is maintained even within the harsh immunosuppressive tumor microenvironment. Together, these data affirm our conviction in WU-NK-101 as a best-in-class allogeneic NK cell therapy. We are eager to continue development of WU-NK-101 and expect to advance into an initial clinical trial for patients with relapsed or refractory (r/r) AML followed by additional studies in solid tumor indications."

Today’s presentation highlighted the following:

WU-NK-101 cells have a unique CIML phenotype with improved activation, metabolic flexibility, and cytotoxicity compared to conventional natural killer cells (cNK).

In vivo activity of WU-NK-101 was confirmed in an AML THP-1 xenograft model, where both single- and multi-dose regimens effectively reduced tumor burden relative to vehicle controls. The data support a planned clinical trial of WU-NK-101 for patients with r/r AML.

WU-NK-101 also overcomes several limitations associated with NK cell therapy in solid tumors, with key features including enhanced metabolic fitness and adaptability and enhanced functionality in immunosuppressive TME conditions compared to cNK—functional characteristics supporting further development of WU-NK-101 in solid tumor indications.

The details of Wugen’s poster presentation at EHA (Free EHA Whitepaper) are as follows:

Title: WU-NK-101, An Allogeneic Memory NK Cell, for the Treatment of Relapse or Refractory (R/R) Acute Myeloid Leukemia (AML)
Session date and time: Friday, June 10, 2022, from 4:30 – 5:45 p.m. CEST
Abstract Number: P1426
Presenting Author: Jan Davidson-Moncada, M.D., Ph.D., Chief Medical Officer, Wugen

Additional meeting information can be found at www.ehaweb.org/congress.

About WU-NK-101

WU-NK-101 is a novel immunotherapy harnessing the power of memory natural killer (NK) cells to treat liquid and solid tumors. Memory NK cells are hyper-functional, long-lasting immune cells that exhibit enhanced anti-tumor activity and a cytokine-induced memory-like (CIML) phenotype. This rare cell population has a superior phenotype, proliferation capacity, and metabolic fitness that makes it better suited for cancer therapy than other NK cell therapies. Wugen is applying its proprietary MonetaTM platform to advance WU-NK-101 as a commercially scalable, off-the-shelf cell therapy for cancer. WU-NK-101 is currently in development for acute myelogenous leukemia (AML) and solid tumors.

On June 10, 2022 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported a poster presentation of preclinical and clinical data on VIP152, the Company’s PTEFb/CDK9 inhibitor, at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Congress, being held virtually and in Vienna, Austria from June 9-12, 2022 (Press release, Vincerx Pharma, JUN 10, 2022, View Source [SID1234615882]).

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The EHA (Free EHA Whitepaper) poster presents data from a high-grade B-cell lymphoma (HGBL) patient with a treatment-related decrease in circulating tumor TP53 mutation and preclinically demonstrates sensitivity of cells derived from chronic lymphocytic leukemia (CLL) patients relapsed after ibrutinib and venetoclax to VIP152 regardless of their TP53 mutation status. "In a pooled analysis of 57 patients with solid or hematologic malignancies, our findings demonstrate that VIP152 did not prolong the QTc interval, which is indicative of a favorable cardiac safety profile and clearly differentiates CDK9 inhibition from the recently reported cardiac toxicity of MCL1 inhibitors," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx. "Compared with other CDK9 inhibitors, VIP152 was the most selective CDK9 inhibitor and had the most robust MYC mRNA downregulation. We believe the high selectivity of VIP152 affords a manageable safety profile, based on the overall patient safety data we shared earlier this week. Additionally, our data showed reproducible reductions in MYC, MCL1, and PCNA mRNA in the blood of patients with various types of lymphoma after VIP152 treatment. These data support the utility of a selective CDK9 inhibitor for the treatment of patients with hematologic malignancies," added Dr. Hamdy.

The EHA (Free EHA Whitepaper) poster also shares new data for 5 lymphoma patients: 3 with HGBL, 1 double expressor diffuse large B-cell lymphoma (DLBCL) and 1 CLL patient from 2 ongoing phase 1 trials. The safety, treatment duration, pharmacokinetics (PK), and progressive disease (PD) were pooled with 7 previously reported HGBL patients for a total of 12 lymphoma patients shown in the presentation. "Two patients with double-hit DLBCL achieved complete remission for 3.5 and 2.5 years and have remained in remission nearly two years after stopping therapy. In addition, the first patient with CLL—who had failed BTK inhibitors and venetoclax—to be treated with a low dose (15 mg) of VIP152 showed initial evidence of clinical activity by physical exam and laboratory parameters," added Dr. Hamdy. "VIP152 also showed a favorable safety profile in lymphoma patients, with manageable neutropenia. The once-weekly VIP152 dosing regimen continues to allow for recovery of neutrophils before the next dose. The results presented at EHA (Free EHA Whitepaper), combined with the totality of preclinical and clinical data generated in our programs to date, support our recent strategic decision to prioritize our VIP152 clinical program on double-hit DLBCL and CLL. We continue to be excited about VIP152 and look forward to advancing our development program with the goal of delivering new treatment options for these patients."

Key Presentation Highlights:

Poster presentation, titled, "VIP152 is a novel CDK9 inhibitor with improved selectivity, target modulation, and cardiac safety in patients with lymphoma," presented by Melanie Frigault, Ph.D., Vice President of Translational Medicine, Vincerx, include:

A KINOMEscan assay revealed a range of ‘hits’ with VIP152 compared with other CDK9 inhibitors (fadraciclib, alvocidib, KB-0742, and AZD4573). In depth evaluation of all potential hits was performed by Kd determination. Kd values showed VIP152 as the most selective CDK9 inhibitor in the clinic today. In the presence of low ATP, VIP152 has an IC50 value of 4.5 nM, and low nanomolar potency was also maintained in the presence of high ATP. The VIP152 IC50 of 4.5 nM was maintained for 15 to 20 hours in the plasma of patients treated at the current clinical dose of 30 mg. Therefore, VIP152 is a highly potent inhibitor of CDK9 kinase activity even in the presence of high ATP concentrations. These data show that physiologically relevant levels of VIP152 are achieved in patients with the 30-mg dose.
In vitro VIP152 treatment led to the most robust downregulation of MYC mRNA expression, observed by a downregulation of 85% genes in two DLBCL cell lines, SU-DHL-4 and SU-DHL-10, compared with atuveciclib (76%) and KB-0742 (68%).
Pooled cardiac safety data from 57 patients demonstrated that VIP152 does not prolong QTc interval after single or multiple doses (5-30 mg).
VIP152 cytotoxicity was evaluated in CRISPR/Cas9 edited CLL cells with homozygous TP53 mutations and showed that wild type and TP53 mutant cell lines were sensitive to VIP152 treatment at 0.5 and 1.0 µM. In vitro treatment of CLL patient-derived cells showed a concentration-dependent reduction in cell viability regardless of number of lines of prior therapy including cells from patients who had relapsed or were refractory to ibrutinib or venetoclax therapy.
This presentation includes new data from five patients (n=3 with HGBL, n=1 double-hit DLBCL, and n=1 CLL). The safety, treatment duration, pharmacokinetics (PK), and progressive disease (PD) were pooled with 7 previously reported HGBL patients for a total of 12 lymphoma patients shown in the presentation. Duration of treatment for this cohort ranges from 2 weeks to over 3 years. Of the 12 total treated patients, five were evaluable for best overall response. Of these, two patients with double-hit DLBCL achieved complete remission and remain in remission nearly two years after stopping therapy, while others stopped treatment due to clinical or radiographic progression; and, in one case due to investigator decision.
The absolute neutrophil count was measured at each treatment visit. Our data show that once weekly dosing of VIP152 allows for the recovery of neutrophils before the next dose. Neutropenia was considered monitorable and manageable with supportive care.
Blood-based PD effect showed a robust down-modulation of MYC, MCL1 and PCNA mRNA in all 11 patients analyzed. Circulating tumor DNA (ctDNA) changes were monitored in three newly reported patients. In one patient, ctDNA reduction in TP53 mutation, and in CDK6 and MYC copy number was observed after three weeks of VIP152 treatment. ctDNA is currently being investigated as a non-invasive tool to aid with predicting outcomes to treatment in patients with high-risk B-cell lymphoma (Meriranta Blood 2022).
Clinical evaluation of VIP152 is currently ongoing in two phase 1 trials in patients with solid tumors or aggressive NHL (NCT02635672), and with CLL and Richter Syndrome (NCT04978779). The poster can be accessed on the presentations section of the Vincerx website.