On December 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 data update from the ongoing phase 1/2 study of the Company’s lead innate cell engager (ICE) AFM13 precomplexed with cord blood-derived natural killer (cbNK) cells in patients with CD30-positive relapsed or refractory Hodgkin and Non-Hodgkin lymphomas (Press release, Affimed, DEC 10, 2022, View Source [SID1234625067]). The results are being presented today at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by principal investigator Yago Nieto, M.D., Ph.D., Professor of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center. Results from the study continue to demonstrate high objective and complete response rates with a well-tolerated safety profile.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In 31 patients with Hodgkin lymphoma treated at the RP2D, an ORR of 97% and a CR rate of 77% were observed. In four non-Hodgkin lymphoma patients treated at the RP2D, three objective responses, including one CR in a patient with peripheral T-cell lymphoma, were observed. Across all 35 patients treated at the RP2D, a 94% ORR and a CR rate of 71% were observed.

"It’s impressive that we continue to see these response rates in a patient population that has exhausted all other treatment options. As a physician, when I consider that all patients in this study did not respond to their previous line of treatment, these results are especially meaningful," said Dr. Andreas Harstrick, Chief Medical Officer at Affimed.

Duration of response (DOR) continues to be monitored, and key observations as of the cutoff date include:

63% of patients with at least 6 months follow-up after initial infusion (n=24) remain in CR for at least 6 months
18 of 33 responders at the RP2D remain in response as of the cutoff date, including 17 of 25 patients with a CR
Five patients treated at the RP2D had their response consolidated with a stem cell transplant
The treatment continues to be well tolerated in the larger patient population, with minimal side effects beyond the expected myelosuppression from the preceding lymphodepleting chemotherapy. No instances of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft versus host disease were observed. There were 20 infusion-related reactions in 294 infusions (6.8%) of AFM13 alone and one infusion-related reaction in 99 infusions (1%) of the cord blood-derived NK cells precomplexed with AFM13. No dose-limiting toxicities were encountered.

"These data further confirm that combining our AFM13 innate cell engager with cord blood-derived natural killer cells has the potential to provide a truly transformative treatment for patients with limited therapeutic options," commented Dr. Adi Hoess, Chief Executive Officer at Affimed. "Our focus and commitment together with our new partner Artiva is expected to bring AFM13 in combination with NK cells to the market as quickly as possible for the benefit of patients with CD30-positive lymphomas."

AFM13, a bispecific tetravalent ICE molecule, is designed for high affinity binding, both to CD16A on NK cells and macrophages, and to CD30 on lymphoma cells.

Oral Presentation Details

Title: Innate Cell Engager AFM13 Combined with Preactivated and Expanded Cord Blood-Derived NK Cells for Patients with Double Refractory CD30+ Lymphoma
Session: Cellular Immunotherapies: Early Phase and Investigational Therapies: Lymphoma
Presentation Date & Time: Saturday, December 10, 2022, 1:15 p.m. CST
Location: Ernest N. Morial Convention Center, La Nouvelle Orleans Ballroom AB

Investor Event, Conference Call and Webcast Information

Affimed will host an investor event to review AFM13 clinical data and development plans in CD30-expressing malignancies. The investor event will take place in-person and virtually and a webcast of the event will be available in the "Webcasts" section on the "Investors" page of Affimed’s website at View Source To access the event via phone, please dial +1 (929) 205-6099 for U.S. callers, or +44 (203) 481-5240 for international callers, and reference meeting ID 847 4106 6227 approximately 15 minutes prior to the call. To reserve your place in the live event, please contact Alex Fudukidis via e-mail at [email protected]. A replay of the webcast/call will be archived on Affimed’s website for 30 days after the call.

About the AFM13-104 Phase 1/2 Study

The University of Texas MD Anderson Cancer Center is studying AFM13 in an investigator-sponsored phase 1/2 trial in combination with cord blood-derived allogeneic NK cells in patients with recurrent or refractory CD30-positive lymphomas. The study is a dose-escalation trial of precomplexed NK cells, followed by an expansion phase recruiting up to 40 patients with r/r CD30 positive lymphomas at the RP2D of 1×108 NK cells/kg. Each treatment cycle consists of lymphodepleting chemotherapy with fludarabine (30 mg/m² per day) and cyclophosphamide (300 mg/m² per day) followed two days later by a single infusion of cytokine-preactivated and expanded cord blood-derived NK cells that are pre-complexed with AFM13. Three weekly infusions of AFM13 (200 mg) monotherapy are subsequently administered and responses are assessed by the investigator on day 28 by FDG-PET.

MD Anderson has an institutional financial conflict of interest with Affimed related to this research and has therefore implemented an Institutional Conflict of Interest Management and Monitoring Plan. Additional information about the study can be found at www.clinicaltrials.gov (NCT04074746). As of the cut-off date, 41 patients with relapsed or refractory CD30-positive Hodgkin and Non-Hodgkin lymphoma were treated in the study, all of whom were evaluable for response. The patients treated in the study have received a median of seven prior lines of therapy. After the first 13 patients treated at the RP2D, the protocol was amended to allow patients to receive up to 4 cycles, whereas previously patients were only eligible for 2 cycles.

About AFM13

AFM13 is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma (REDIRECT). Additional details can be found at www.clinicaltrials.gov (NCT04101331).

On December 10, 2022 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported final safety and efficacy results from firstMIND, a Phase 1b, open-label, randomized safety study combining tafasitamab or tafasitamab plus lenalidomide with standard R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) (Press release, MorphoSys, DEC 10, 2022, View Source [SID1234625066]). Additional analyses highlighted the prognostic potential of sensitive circulating tumor (ct) DNA minimal residual disease (MRD) assays in patients with DLBCL after first-line therapy. These results are being presented during oral and poster sessions on December 10, 2022, at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in New Orleans, Louisiana.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Tafasitamab, marketed in the U.S. as Monjuvi and outside the U.S. by Incyte as Minjuvi, is a CD19 targeting immunotherapy. Tafasitamab received an accelerated approval and conditional approval by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively, for patients with certain types of DLBCL that has come back (relapsed) or that did not respond to previous treatment (refractory) and who are not eligible to receive a stem cell transplant.

"The final analysis from firstMIND underscores the therapeutic potential of tafasitamab in combination with lenalidomide added on to standard R-CHOP therapy for patients with newly diagnosed DLBCL," said Greg S. Nowakowski, M.D., Professor of Medicine and Oncology at the Mayo Clinic and lead investigator for the firstMIND trial. "This regimen, which is also being investigated in the Phase 3 frontMIND trial, represents an ongoing effort to address a critical need in patients with high-risk DLBCL, many of whom relapse after current first-line therapy. I am encouraged by the results from firstMIND and eagerly anticipate the Phase 3 data on the combined efficacy of tafasitamab, lenalidomide and R-CHOP in newly diagnosed patients with DLBCL."

The final analysis of firstMIND demonstrated an overall response rate at the end of treatment of 75.8% for patients treated with tafasitamab plus R-CHOP (n=33) and 81.8% for patients treated with tafasitamab, lenalidomide and R-CHOP (n=33). In the tafasitamab, lenalidomide and R-CHOP arm, 24-month progression-free survival (PFS) and overall survival (OS) rates were 76.8% and 93.8%, respectively. PFS and OS rates were 73.6% and 95.2%, respectively, for patients with high-intermediate to high-risk DLBCL (International Prognostic Index [IPI] 3-5) treated with tafasitamab, lenalidomide and R-CHOP (n=22). Improved PFS was observed in MRD-negative patients compared with MRD-positive patients.

The most common hematological treatment emergent adverse events in both patients treated with tafasitamab plus R-CHOP and patients treated with tafasitamab, lenalidomide and R-CHOP were neutropenia (60.6% and 84.8%, respectively), anemia (51.5% and 60.6%), thrombocytopenia (21.2% and 42.4%) and leukopenia (30.3% and 27.3%), respectively. Rates of febrile neutropenia were equal (18.2%) in both arms. Non-hematological adverse events were well balanced between arms and were mostly grades 1 and 2. No unexpected toxicities or new safety signals were identified in the final analysis.

A second poster presentation and an oral presentation both demonstrate the potential of sensitive ctDNA MRD assays to predict PFS outcomes following first-line treatment in patients with DLBCL. In the poster presentation, negative MRD as detected by next generation sequencing detection of ctDNA after treatment with tafasitamab in combination with lenalidomide and R-CHOP in the firstMIND study was associated with a significant improvement in PFS (p=0.008). One of 12 patients who were MRD-negative after treatment had developed disease progression by the time of data cutoff, when all patients had completed 18 months of post-treatment follow-up.

The oral presentation highlighted the prognostic utility of sensitive ctDNA MRD assays in a meta-analysis of five prospective studies of first-line treatment regimens for large B-cell lymphomas. Achievement of MRD negativity after any of the first three cycles of treatment was strongly prognostic for PFS (p=0.0003), and failure to achieve MRD negativity by the end of treatment was associated with the highest risk for progression. Detection of ctDNA MRD at levels below 1 in 10,000 (0.01%) was essential to achieve 99% sensitivity.

"These new data suggest that assays that can better detect minimal residual disease carry important prognostic value and may serve as surrogate markers for clinical benefit in future lymphoma trials," said Dr. Tim Demuth, Chief Research and Development Officer at MorphoSys. "These insights, along with the final results from firstMIND and growing body of data supporting Monjuvi in second-line therapy, give us greater understanding of how to improve outcomes at diagnosis or first relapse. We are eager to learn through frontMIND about the potential of tafasitamab plus lenalidomide to augment a standard of care in first-line therapy for patients newly diagnosed with high-intermediate and high-risk DLBCL."

On December 10, 2022 argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, reported that data from its Phase 3 ADVANCE trial will be presented during the plenary session at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in New Orleans, LA (Sunday, December 11, 2022, 2-4pm CT) (Press release, argenx, DEC 10, 2022, View Source [SID1234625065]). The ADVANCE study is the first of two registrational trials evaluating the efficacy, safety and tolerability of VYVGART (efgartigimod alfa-fcab) for the treatment of adult patients with primary ITP.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very excited to present our ITP data during the plenary session at ASH (Free ASH Whitepaper), giving us the opportunity to highlight the potential of a new approach to treating this rare, complex disease. People living with ITP need more treatment options with new mechanisms of action that target the underlying biology of the disease, and we look forward to sharing our findings in helping to address this gap with the broader ITP community," said Luc Truyen, M.D., Ph.D., Chief Medical Officer, argenx. "ADVANCE is the second Phase 3 clinical trial in which VYVGART has demonstrated a strong clinical benefit, underscoring our belief in the breadth of potential for this asset in a range of high-need IgG-mediated autoimmune diseases."

Topline data from ADVANCE were reported in May 2022. The trial met its primary endpoint demonstrating a significantly higher proportion (p=0.0316) of VYVGART-treated chronic ITP patients achieved a sustained platelet response (17/78; 21.8%) compared to placebo (2/40; 5%). Sustained platelet response was defined as having platelet counts greater than or equal to 50×109/L on at least four of the last six scheduled visits between weeks 19 and 24 of treatment. Key platelet-derived secondary endpoints (first two secondary endpoints) were also met. VYVGART was well-tolerated in this 24-week chronic dosing study and the observed safety and tolerability profile was consistent with previous clinical trials.

Highlights From ASH (Free ASH Whitepaper) Plenary Session

Early, sustained platelet count increase: 38% of VYVGART-treated participants reached a platelet count of 30×109/L platelets at week 1 compared to 11.1% placebo

Sustained response across all subgroups: subgroup analyses (including on prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics) of patients who achieved the primary endpoint all favored VYVGART over placebo

International Working Group (IWG) responder status: VYVGART resulted in higher responses than placebo on analysis of IWG response criteria

51.2% (44/86) of VYVGART-treated patients achieved an IWG response compared to 20% placebo
IWG responders were defined as having a platelet count of at least 30×109/L, a two-fold increase in platelet count from baseline, and the absence of bleeding for two separate, consecutive weekly visits

Extent of disease control: VYVGART-treated patients experienced substantially more weeks with disease control, with 44% sustaining response for at least 5-9 weeks (12% placebo), 28% for at least 10-14 weeks (0% placebo), and 17% for at least 15-19 weeks (0% placebo)

Sustained platelet count response was achieved in 90% (9/10) of VYVGART responders who switched from weekly to every other week dosing (after surpassing platelet counts of 100×109/L for three out of four consecutive visits); one placebo patient switched to biweekly dosing but did not achieve a sustained platelet count response
Key pharmacodynamic parameters: total IgG levels were reduced in VYVGART-treated patients throughout observation period, supporting proposed mechanism of action
Mean IgG levels decreased steadily over the first 4 weeks of treatment; baseline remained >60% throughout the trial
Consistent safety profile: continuous weekly or biweekly dosing was well-tolerated and did not result in any new safety signals from those reported from previous trials

"I am honored to deliver this oral presentation on behalf of my co-investigators at ASH (Free ASH Whitepaper), one of the most prestigious hematology meetings, to provide my peers with additional details on the promising results from the ADVANCE study," stated Catherine Broome, M.D., Associate Professor of Medicine at Georgetown University Lombardi Comprehensive Cancer Center, and Principal Investigator in the ADVANCE trial. "Along with the previously reported positive efficacy, safety and tolerability data from the trial, further analyses show efgartigimod demonstrated rapid and sustained reduction in IgG autoantibodies, which correlated with platelet count response, as well as consistent improvement over placebo across each evaluated weekly timepoint. The data generated to date give us optimism that this therapy could provide a new tool in the treatment of ITP, and we look forward to seeing results from the subcutaneous study in 2023."

The Phase 3 ADVANCE IV trial is the first of two registrational trials being conducted as part of the ongoing ITP development program. ADVANCE-SC is evaluating SC VYVGART for the treatment of primary ITP. Topline data from the ADVANCE-SC study are expected in the second half of 2023.

Phase 3 ADVANCE Trial Design
The Phase 3 ADVANCE trial was a randomized, double-blind, placebo-controlled, multicenter, global trial evaluating the efficacy and safety of VYVGART in adult patients with chronic or persistent primary ITP. ​A total of 131 adult patients with primary ITP in North America, Europe and Japan enrolled in the trial and received VYVGART or placebo for a total of 24 weeks as part of the primary trial. Enrolled patients had a confirmed ITP diagnosis and a mean entry platelet count of less than 30×109/L. Patients were on a stable dose of at least one ITP treatment prior to randomization and had received at least one prior therapy. Concomitant medications permitted included corticosteroids, nonsteroidal immunosuppressive drugs, fostamatinib or TPO-RAs. If patients were on ‘watch and wait’ at baseline, they had to have received at least 2 prior treatments for ITP. ​

Patients were randomized in a 2:1 ratio to receive VYVGART or placebo for a total of 24 weeks as part of the primary trial. Randomized patients received weekly infusions from weeks 1-4 and were eligible to adjust frequency to bi-weekly depending on platelet count. Administration frequency was fixed from study visits 16-24. ​The primary endpoint was measured by the proportion of patients with chronic ITP with a sustained platelet count response defined as achieving platelet counts of greater than or equal to 50×109/L for at least four of the last six scheduled visits between weeks 19 and 24. Patients who received rescue therapy at week 12 or later, or for whom dose and/or frequency of concurrent ITP therapies increased at week 12 or later, were considered non-responders. ​Key secondary endpoints included extent of disease control over 24-week treatment period, proportion of overall population with sustained platelet count response, incidence and severity of WHO-classified bleeding events and an extended primary endpoint analysis between weeks 17 and 24.

See the full Prescribing Information for VYVGART in the U.S., which includes the below Important Safety Information. For more information related to VYVGART in Japan, visit argenx.jp.

Important Safety Information for VYVGART (efgartigimod alfa-fcab) intravenous (IV) formulation (U.S. prescribing information)

What is VYVGART (efgartigimod alfa-fcab)?
VYVGART is a prescription medicine used to treat a condition called generalized myasthenia gravis, which causes muscles to tire and weaken easily throughout the body, in adults who are positive for antibodies directed toward a protein called acetylcholine receptor (anti-AChR antibody positive).

What is the most important information I should know about VYVGART?
VYVGART may cause serious side effects, including:

Infection. VYVGART may increase the risk of infection. In a clinical study, the most common infections were urinary tract and respiratory tract infections. More patients on VYVGART vs placebo had below normal levels for white blood cell counts, lymphocyte counts, and neutrophil counts. The majority of infections and blood side effects were mild to moderate in severity. Your health care provider should check you for infections before starting treatment, during treatment, and after treatment with VYVGART. Tell your health care provider if you have any history of infections. Tell your health care provider right away if you have signs or symptoms of an infection during treatment with VYVGART such as fever, chills, frequent and/or painful urination, cough, pain and blockage of nasal passages/sinus, wheezing, shortness of breath, fatigue, sore throat, excess phlegm, nasal discharge, back pain, and/or chest pain.
Undesirable immune reactions (hypersensitivity reactions). VYVGART can cause the immune system to have undesirable reactions such as rashes, swelling under the skin, and shortness of breath. In clinical studies, the reactions were mild or moderate and occurred within 1 hour to 3 weeks of administration, and the reactions did not lead to VYVGART discontinuation. Your health care provider should monitor you during and after treatment and discontinue VYVGART if needed. Tell your health care provider immediately about any undesirable reactions.
Before taking VYVGART, tell your health care provider about all of your medical conditions, including if you:

Have a history of infection or you think you have an infection.
Have received or are scheduled to receive a vaccine (immunization). Discuss with your health care provider whether you need to receive age-appropriate immunizations before initiation of a new treatment cycle with VYVGART. The use of vaccines during VYVGART treatment has not been studied, and the safety with live or live-attenuated vaccines is unknown. Administration of live or live-attenuated vaccines is not recommended during treatment with VYVGART.
Are pregnant or plan to become pregnant and are breastfeeding or plan to breastfeed.

Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the common side effects of VYVGART?
The most common side effects of VYVGART are respiratory tract infection, headache, and urinary tract infection.

These are not all the possible side effects of VYVGART. Call your doctor for medical advice about side effects. You may report side effects to the US Food and Drug Administration at 1-800-FDA-1088.

Please see the full Prescribing Information for VYVGART and talk to your doctor.

About American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition
The 64th ASH (Free ASH Whitepaper) Annual Meeting and Exposition is scheduled to take place December 10-13, 2022 at the Ernest N. Morial Convention Center in New Orleans, Louisiana. This in-person event will be broadcast virtually. The ASH (Free ASH Whitepaper) 2022 Annual Meeting abstracts are available at: View Source

About Immune Thrombocytopenia (ITP)
Immune thrombocytopenia (ITP) is an autoimmune disorder where immunoglobulin G (IgG) autoantibodies destroy platelets and reduce platelet production, which can lead to an increased risk of excessive bleeding and bruising. In severe cases, frequent bleeding events can cause anemia or even brain hemorrhage in rare cases. ITP is also associated with debilitating fatigue and significant impacts on mental health, including anxiety, fear and depression. Many ITP patients are inadequately controlled on current therapies so there remains a significant unmet need for additional treatment options.

About VYVGART (efgartigimod alfa-fcab)
VYVGART is a human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating immunoglobulin G (IgG) autoantibodies. It is the first and only approved FcRn blocker. VYVGART is approved in the United States and Europe for the treatment of adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive and in Japan for the treatment of adults with gMG who do not have sufficient response to steroids or non-steroidal immunosuppressive therapies (ISTs). VYVGART is being studied in adults with primary immune thrombocytopenia (ITP) and other IgG autoantibody-mediated diseases.

On December 10, 2022 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported that its research collaborators at Fred Hutchinson Cancer Research Center presented data from the Compassionate Use Program on anti-leukemic activity of STRO-002, a novel folate receptor-α (FR-α) targeting ADC, in pediatric patients with relapsed/refractory CBFA2T3-GLIS2 (CBF/GLIS) acute myeloid leukemia (AML), commonly known as RAM phenotype AML, in an oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2022) in New Orleans, LA (Press release, Sutro Biopharma, DEC 10, 2022, View Source [SID1234625064]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

STRO-002 was provided to 17 pediatric patients with CBF/GLIS subtype AML on a compassionate use basis. Clinical results from these patients were compiled by Sutro and presented as an oral presentation by Soheil Meshinchi, M.D., Ph.D., Professor, Clinical Research Division, at Fred Hutchinson Cancer Research Center; Professor, Division of Pediatric Hematology-Oncology, at the University of Washington School of Medicine; and Principal Investigator for the program, titled, "Anti-Leukemic Activity of STRO-002 a Novel Folate Receptor-α (FR-α)-Targeting ADC in Relapsed/Refractory CBFA2T3-GLIS2 AML."

"I am heartened to observe such encouraging results in children with this rare disease who have a dismal prognosis with conventional therapies and no treatment options," commented Dr. Meshinchi. "The clinical responses to STRO-002 in this group of patients who have relapsed or are refractory to standard of care treatments, suggest that this drug is particularly promising and provides hope for patients and families impacted by this devastating disease."

CBF/GLIS subtype AML is a rare, serious and life-threatening disease affecting pediatric patients with a median age of 1.5 years1 and the prevalence of CBF/GLIS in childhood is approximately 1 to 3% of pediatric AML cases1. These high-risk children with AML have an extremely poor prognosis with a 5-year overall survival of approximately 20%2. Patients are highly refractory to standard of care therapies and there are currently no approved therapies specifically targeting CBF/GLIS subtype AML.

Recent studies have shown that FOLR1, which encodes for FolRα, is silent in normal hematopoiesis, but is uniquely induced by the CBF/GLIS fusion3. Preclinical data presented last year at ASH (Free ASH Whitepaper) 2021 demonstrated that patients with CBF/GLIS AML may benefit from STRO-002.

"We are encouraged by the positive results of our compassionate use program in children with a rare form of AML with STRO-002, which was recently granted Orphan Drug Designation by FDA in this patient population," said Bill Newell, Sutro’s Chief Executive Officer. "These results underscore our confidence in the efficacy and tolerability for STRO-002, in addition to the development path forward for patients with ovarian and endometrial cancers."

ASH 2022 Data Highlights:

17 pediatric patients were treated with STRO-002 on a compassionate use basis.
All 17 patients were relapsed/refractory to standard of care AML treatments. The median age of the patients is two years old and the median number of prior therapies is two. Eight of the patients had previously undergone a stem cell transplant (SCT).
STRO-002 was well-tolerated as a monotherapy agent and in combination with standard of care therapies.
In the 17 patients treated, Best Overall Response (BOR) includes eight patients with complete remission (CR), of which seven patients were minimal residual disease (MRD) negative.
47% of the patients achieved complete remission and 53% of the patients achieved partial response or stable disease.
Responders were seen in various settings including in patients with or without prior stem cell transplant and in monotherapy or in combination with cytotoxic therapy.
The presentation will be made available today in the "Clinical/Scientific Presentation and Publication Highlights" section of Sutro Biopharma’s website at www.sutrobio.com and a whitepaper with details about this rare indication and Sutro’s compassionate use program is available on the Company’s website here.

*1: National Institutes of Health [NIH], 2022; Quessada et al 2021; Masseti et al 2019
*2: Smith JL, et al. Comprehensive Transcriptome Profiling of Cryptic CBFA2T3-GLIS2 Fusion-Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study. Clin Cancer Res. 2020 Feb 1;26(3):726-737. doi: 10.1158/1078-0432.CCR-19-1800. Epub 2019 Nov 12. PMID: 31719049; PMCID: PMC7002196.
*3: Le Q, et al. Targeting FOLR1 in High-Risk CBFA2T3-GLIS2 AML with Stro-002 FOLR1-Directed Antibody-Drug Conjugate, Blood, Volume 138, Supplement 1, 2021, Page 209, ISSN 0006-4971, View Source

About STRO-002

STRO-002 is an optimized FolRα-targeting antibody-drug conjugate (ADC) with a drug-antibody ratio (DAR) of 4, which is precisely conjugated using non-natural amino acids attached to stable protease-cleavable linkers and hemiasterlin-derivative warheads. STRO-002 potentially has a dual mechanism of action against the tumor through cytotoxic killing and through inducing immunogenic cell death. STRO-002 was designed with Sutro’s proprietary cell-free protein synthesis and site-specific conjugation platform, which enables precise design, rapid empirical optimization, and manufacture of site-specific homogenous ADCs.

On December 10, 2022 -Orum Therapeutics, a private biotechnology company pioneering the development of tumor-directed targeted protein degraders (TPDs), reported the presentation of positive preclinical data for ORM-6151, a first-in-class, anti-CD33 antibody-enabled GSPT1 degrader for acute myeloid leukemia (AML), at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2022) Annual Meeting & Exposition taking place December 10-13 in New Orleans and virtually (Press release, Orum Therapeutics, DEC 10, 2022, View Source [SID1234625062]). ORM-6151 is the second drug candidate from Orum’s Dual-Precision Targeted Protein Degradation (TPD2 TM) approach, which combines the catalytic mechanism of TPDs with the precision of tumor-targeting therapeutic antibodies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These data demonstrate we can increase the therapeutic index to improve the efficacy and tolerability of targeted protein degrader therapies with our ‘TPD-squared’ approach"

Tweet this
The data show that ORM-6151 has picomolar potency and efficacy superior to clinically equivalent doses of CC-90009, a small-molecule GSPT1 degrader, or Mylotarg, an FDA-approved treatment for AML, in CD33-expressing cell lines and primary relapsed/refractory AML patient blasts. In a clinically relevant animal model of AML, a single treatment of ORM-6151 at doses as low as 1 mg/kg, compared to a clinically equivalent dose of CC-90009, demonstrated superior tumor growth inhibition and correlated with the degree and duration of GSPT1 depletion. ORM-6151 also had robust activity in Mylotarg-resistant cell lines and exhibited minimal cytotoxic activity to healthy hematopoietic progenitor cells compared to CC-90009 or Mylotarg.

"These data demonstrate we can increase the therapeutic index to improve the efficacy and tolerability of targeted protein degrader therapies with our ‘TPD-squared’ approach," said Peter U. Park, Ph.D., Chief Scientific Officer of Orum Therapeutics. "We believe that ORM-6151 via targeted tumor delivery has the potential to provide an improved therapeutic option in AML that appropriately balances efficacy with safety and tolerability of a clinically validated GSPT1 degradation mechanism. We look forward to continuing development of ORM-6151 with a goal of filing an Investigational New Drug application in the first half of 2023."

The poster can be viewed in the poster hall and via the virtual meeting platform for registered attendees. Details of the presentation are as follows, and the abstract can be viewed by clicking here.

Title: ORM-6151: A First-in-Class, Anti-CD33 Antibody-Enabled GSPT1 Degrader for AML
Publication Number: 1319
Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster I
Session Date: Saturday, December 10
Presentation Time: 5:30 PM to 7:30 PM CST
Location: Ernest N. Morial Convention Center, Hall D

About Orum’s GSPT1 Platform Using the TPD² Approach

Orum’s GSPT1 platform uses the Company’s unique Dual-Precision Targeted Protein Degradation (TPD²) approach to build novel targeted protein degraders combined with the precise tumor cell delivery mechanisms of antibodies to generate innovative, first-in-class, cell-specific TPDs for the treatment of cancer. The company has developed new molecular glue degrader payloads to specifically degrade an intracellular target protein within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, the payloads are designed to be delivered specifically to cancer cells and degrade the intracellular target protein GSPT1 and cause tumor cell death.