On April 8, 2022 Shanghai Junshi Biosciences Co., Ltd ("Junshi Biosciences", HKEX: 1877; SSE: 688180) and Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) reported the results of the prespecified final progression-free survival ("PFS") analysis and the interim overall survival ("OS") analysis of the JUPITER-02 study (NCT03581786), a pivotal Phase 3 trial in first-line treatment of recurrent or metastatic nasopharyngeal carcinoma ("NPC") (Press release, Coherus Biosciences, APR 8, 2022, View Source [SID1234611698]). The JUPITER-02 results are summarized in a poster presentation at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR").

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In the final PFS analysis, results from JUPITER-02 demonstrated that toripalimab in combination with chemotherapy provided a statistically significant improvement in PFS assessed by the blinded independent review committee ("BIRC") compared to chemotherapy plus placebo, with an improvement in median PFS of 13.2 months (21.4 versus 8.2 months). Furthermore, the addition of toripalimab to chemotherapy provided significant improvements in the secondary endpoints of PFS assessed by the investigator, objective response rate ("ORR") and duration of response ("DoR"), while maintaining a safety profile consistent with that in previously reported toripalimab clinical trials. Although the median OS ("mOS") was not yet mature in either arm, the interim OS analysis showed a trend favoring the toripalimab arm and will be formally tested in a prespecified final analysis.

"First-line treatment options for advanced NPC remain limited for this difficult-to-treat tumor, resulting in poor outcomes for patients due to therapeutic resistance to chemotherapy, which is the current standard of care," said Professor Ruihua Xu, the poster’s corresponding author from Sun Yat-sen University Cancer Center (SYSUCC). "The JUPITER-02 results validate the potential advancement that toripalimab in combination with chemotherapy would represent as a new standard-of-care first-line therapy for patients with advanced NPC."

Rosh Dias, MD, MRCP, Coherus’ Chief Medical Officer, added, "Innovative immuno-oncology approaches including anti-PD-1 monoclonal antibody treatments represent a promising new option for advanced nasopharyngeal carcinoma, for which there are currently no approved immuno-oncology treatments in the United States. The significant improvement demonstrated in JUPITER-02 with the combination of toripalimab and chemotherapy across key clinically meaningful endpoints compared to chemotherapy alone supports its use as a potential new standard of care treatment option for advanced NPC."

"We are excited that the updated results from JUPITER-02 confirm that the addition of toripalimab to chemotherapy significantly extends the median PFS of patients with advanced NPC by more than a year," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences. "We believe that toripalimab can revolutionize the treatment of advanced NPC and are working closely with the FDA and our partner, Coherus, to provide the first approved therapy for patients with this rare disease in the U.S."

The United States Food and Drug Administration ("FDA") granted breakthrough therapy designation for toripalimab in combination with gemcitabine and cisplatin as first-line treatment for patients with advanced recurrent or metastatic NPC and for toripalimab monotherapy for second-line or later treatment of recurrent or metastatic NPC after platinum-containing chemotherapy. A biologics license application ("BLA") for these indications is under priority review by the FDA. Coherus and Junshi Biosciences are working closely with the FDA to complete the review process and schedule any required inspections in China.

About JUPITER-02 Study Results

JUPITER-02, conducted in mainland China, Taiwan and Singapore, is the largest Phase 3 clinical study to date to evaluate a checkpoint inhibitor plus chemotherapy for the first-line treatment of recurrent or metastatic NPC. Two hundred eighty-nine patients with advanced NPC, who had received no prior chemotherapy for recurrent or metastatic disease, were randomized 1:1 to receive toripalimab 240 mg or placebo in combination with gemcitabine 1000 mg/m2 (d1, 8) and cisplatin 80 mg/m2 (d1), Q3W followed by toripalimab or placebo monotherapy until disease progression, intolerable toxicity or completion of two years of treatment. PFS and response were assessed by the BIRC and by the investigator per RECIST v1.1. There was one prespecified interim analysis of PFS at 130 (65%) PFS events and a final analysis at 200 PFS events.

At the final PFS analysis (cut-off date June 8, 2021), the median follow-up time was 22.1 months for the toripalimab arm and 21.4 months for the placebo arm.

A summary of the results is as follows:

The addition of toripalimab to gemcitabine-cisplatin ("GP") chemotherapy as first-line treatment for advanced NPC patients provided superior PFS, OS, ORR and DoR than GP chemotherapy alone:
Significant improvement in PFS: mPFS 21.4 vs. 8.2 months, HR=0.52 (95% CI: 0.37, 0.73), P <0.0001.
Significant improvement in ORR: 78.8% vs. 67.1% (P = 0.0221).
Significant improvement in DoR: mDoR 18.0 vs. 6.0 months, HR=0.49, P = 0.0003.
Although mOS was not mature in either arm, a 41% reduction in risk of death was observed in the toripalimab arm over the placebo arm, HR=0.59 (95% CI: 0.37, 0.94), nominal P =0.0238.
The safety profile was consistent with that previously reported in other toripalimab clinical trials with no new safety signals identified with toripalimab added to GP.
About toripalimab

Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promotes the immune system’s ability to attack and kill tumor cells.

More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and European countries. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.

In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). Currently, there are four approved indications for toripalimab in China:

unresectable or metastatic melanoma after failure of standard systemic therapy;
recurrent or metastatic nasopharyngeal carcinoma NPC after failure of at least two lines of prior systemic therapy;
locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy;
in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC.
The first three indications have been included in the National Reimbursement Drug List (NRDL) (2021 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for melanoma and NPC.

In addition, two supplemental New Drug Applications (NDAs) for toripalimab are currently under review by the National Medical Products Administration (NMPA) in China:

in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic ESCC.
in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic NSCLC without EGFR or ALK mutations.
In the United States, the FDA has granted priority review for the toripalimab BLA for the treatment of recurrent or metastatic NPC, an aggressive head and neck tumor which has no FDA-approved immuno-oncology treatment options. The FDA has assigned a Prescription Drug User Fee Act ("PDUFA") target action date for April 2022 for the toripalimab BLA. The FDA granted Breakthrough Therapy designation for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC in 2021 as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC in 2020. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and Orphan Drug Designation for the treatment of esophageal cancer, NPC, mucosal melanoma and soft tissue sarcoma. In 2021, Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple other cancer types.

On April 8, 2022 Genocea Biosciences, Inc. (NASDAQ: GNCA), a biopharmaceutical company developing next-generation neoantigen immunotherapies, reported that clinical, preclinical, and manufacturing data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 beginning today in New Orleans and virtually (Press release, Genocea Biosciences, APR 8, 2022, View Source [SID1234611697]). The presentations include promising initial data from the TiTAN clinical trial for the neoantigen-targeted peripheral T cell (NPT) therapy product candidate GEN-011, results demonstrating successful production of GEN-011 using Genocea’s PLANET manufacturing process, and new preclinical data on Inhibigens, antigens of suppressive immune responses uniquely identifiable by Genocea’s ATLAS platform.

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The Phase 1/2a TiTAN trial investigates the safety, tolerability, T cell persistence and proliferation, and clinical activity of GEN-011 in patients with refractory solid tumors. The study includes two dosing cohorts. Cohort A patients (n=2) received a lower intensity regimen without lymphodepletion with fractional GEN-011 doses monthly, and with post-infusion intermediate dose interleukin-2 (IL-2) (125K IU/kg daily s.c.). In Cohort B, patients (n=3) received GEN-011 as a single infusion after lymphodepletion, followed by IL-2. This Cohort includes one of three escalating lymphodepletion and IL-2 dose regimens, and patients have not yet been dosed at the highest regimen.

The early results presented at AACR (Free AACR Whitepaper) show anti-tumor activity despite the lower intensity regimens and heavily pretreated tumors. Stable disease was seen at the initial Day 57 scan in four of the five patients. While all patients had progressive disease (PD) at their Day 113 scan, three of the five experienced clear biologic changes after infusion. These included palpable improvement in peripheral nodal disease and resolution of severe neuropathy causing arm paralysis and pain in patients with refractory SCCHN. A patient with metastatic non-small cell lung cancer (NSCLC) experienced a 10% reduction in tumor diameters (approx. 30% reduction in volume), also with resolution of tumor associated cough. The potential for drug product proliferation and persistence for months is supported by translational assays, and clinical activity is associated with declines in detectable circulating tumor DNA (ctDNA) after treatment in some patients.

None of the initial patients have experienced dose-limiting toxicities, with no evidence of self-reactivity or autoimmune toxicity. Overall, the range of Grade 2 and Grade 3 treatment emergent adverse events (TEAEs) align with expected toxicity from cell therapy regimens. The poster presentation and additional context are available in the Scientific Resources section of the Genocea website.

Genocea has had a 100% success rate in manufacturing GEN-011 through its PLANET process to date. Of the 17 patient samples entering PLANET, 100% have either successfully yielded a released drug product (14) or are continuing in process (3). Significantly, as a result of continuous process improvements, the next six patients will be dosed with drug products that have a median two-fold increase in cell dose and greater neoantigen specificity and potency.

"Using peripherally derived T cells and our ATLAS bioassay to target specific neoantigens for inclusion or Inhibigen exclusion in GEN-011 is yielding promising early results in patients," said Thomas Davis, MD, Chief Medical Officer of Genocea. "This activity in low intensity regimens shows that the neoantigen targeted cells are recognizing and engaging with the tumor, which is a very encouraging sign of the potential for greater clinical activity in more intense regimens. Additionally, the continued improvements to our PLANET manufacturing process could lead to more clinically meaningful results in this patient population with high unmet need. We are grateful to our trial participants and are excited for more results to come in Q4 this year."

Additional data presented at AACR (Free AACR Whitepaper) highlights ongoing work characterizing inhibitory antigens, or Inhibigens – putatively pro-tumor antigens that are uniquely identifiable by ATLAS and present in nearly every cancer patient profiled by Genocea. With the benefit of ATLAS, Genocea excludes T cells to Inhibigens from GEN-011. A preclinical poster presented at the meeting demonstrates how detrimental these Inhibigens are to the efficacy of cancer therapeutics in mouse models of melanoma and pancreatic cancer.

Genocea is hosting an investor webcast with live Q&A at 4:30 pm ET on Friday, April 8. Dr. Melissa Johnson, Program Director of Lung Cancer Research and the Solid Tumor Immune Effector Cellular Therapy Program at the Sarah Cannon Cancer Institute, will join Genocea leadership to discuss the GEN-011 clinical results and other data being presented at AACR (Free AACR Whitepaper). The live webcast will be available on the Events & Presentations page of the Genocea website, with the recording and poster presentations in the Scientific Resources section immediately following the event.

AACR POSTER SESSION CATEGORY: Phase 1 Adult Clinical Trials
Abstract #CT153
Title: TiTAN: a phase 1 study of GEN-011, a neoantigen-targeted peripheral blood-derived T cell therapy with broad neoantigen targeting
Presenter: Maura Gillison, MD, PhD, MD Anderson Cancer Center
Date: Monday, April 11, 2022
Time: 1:30 p.m. – 5:00 p.m. CT
Clinical Results from 5 initial patients show no dose limiting toxicities and proliferation and persistence of desired effector memory T cells for at least 36 days. As expected from a non-exhausted peripherally-derived T cell product, this persistence supports the biological activity of GEN-011.

AACR POSTER SESSION CATEGORY: Inflammation, Immunity, and Cancer
Abstract #2088
Title: The PLANET manufacturing process reproducibly generates high-quality neoantigen-targeted peripheral T cells (NPTs) for adoptive T cell therapy in the TiTAN clinical trial
Presenter: Harshal Zope, PhD, Genocea Biosciences
Date: Monday, April 11, 2022
Time: 1:30 p.m. – 5:00 p.m. CT
Results of the PLANET manufacturing process show 100% success in the production of a customized drug product for patients, each including exclusively T cells covering 90% of the intended neoantigen targets. The resulting neoantigen-targeted peripheral T cells are non-exhausted, broadly reactive, and include up to 30 characterized neoantigen targets.

AACR POSTER SESSION CATEGORY: Clinical Research Excluding Trials
Abstract #2745
Title: ATLAS-identified Inhibigen-specific responses accelerate tumor growth in mouse melanoma and pancreatic cancer
Presenter: Jessica Flechtner, PhD, Genocea Biosciences
Date: Tuesday, April 12, 2022
Time: 9:00 a.m. – 12:30 p.m. CT
Inhibigens, regardless of antigen type, disrupt an otherwise protective vaccine in mouse models of melanoma. Furthermore, Inhibigens also promote tumor growth in pancreatic cancer models, demonstrating the effect is not cancer type-specific. Transplanting T cells into nude mice confirms that Inhibigen-specific T cells exert this pro-tumor effect.

About GEN-011
GEN-011 is a neoantigen-targeted peripherally derived T cell therapy candidate comprised of autologous CD4+ and CD8+ T cells that are specific for up to 30 ATLAS-identified neoantigens to limit tumor escape. NPTs have minimal bystander, non-tumor-specific cells, and are devoid of Inhibigen-specific cells which may be detrimental to clinical response.

About the GEN-011 TiTAN clinical trial
TiTAN is an open-label, multi-center Phase1/2a trial evaluating safety, tolerability, T cell persistence and proliferation and clinical efficacy of GEN-011. The TiTAN clinical trial is testing two cohorts. Cohort A patients receive a fractionated lower dose regimen of GEN-011 without lymphodepletion and an intermediate IL-2 regimen to maximize the tumor-killing potential of the infused cells. Cohort B patients receive a single high dose administration of GEN-011, along with one of three escalating regimens of lymphodepletion and IL-2.

On April 8, 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 preliminary clinical data on VIP152, the Company’s PTEFb/CDK9 inhibitor, in gynecologic cancer cell lines and in patients with gynecologic malignancies, respectively, at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held virtually and in New Orleans, Louisiana from April 8-13, 2022 (Press release, Vincerx Pharma, APR 8, 2022, View Source [SID1234611694]).

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"The preclinical data presented at AACR (Free AACR Whitepaper) demonstrate sensitivity of gynecologic cancer cell lines with MYC and/or MYCN genetic alterations to VIP152," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx, "Our findings demonstrate that VIP152 monotherapy inhibits tumor growth in an ovarian cancer xenograft model in mice. We believe these preclinical data are noteworthy and translate through to primary tissue samples from patients with ovarian or endometrial cancer showing significant reduction in MYC protein expression ex vivo, and, in the blood of patients with gynecologic cancer, a downregulation of CDK9-regulated genes MYC, MCL1, and PCNA mRNA expression after VIP152 treatment."

"Additionally, our preliminary VIP152 monotherapy clinical results as of March 2022 demonstrated an early signal in patients with gynecologic malignancies who have had multiple lines of prior therapy," continued Dr. Hamdy. "In our ongoing first-in-human study, 3 out of 3 patients with MYC-amplified gynecologic cancer had stable disease at first assessment, as well as 1 out of 4 patients with ovarian cancer unselected for MYC. These results, together with our findings presented at ASH (Free ASH Whitepaper) last year, suggest that VIP152 has the potential to provide new treatment options for patients across various MYC and MCL-1- driven tumor types. We are continuing to enroll patients in our Phase 1b expansion study across multiple tumor types including hematologic malignancies."

Key Presentation Highlights:

Poster presentation, titled, "VIP152, a selective CDK9 inhibitor, demonstrates sensitivity in gynecologic cell lines that are cisplatin sensitive or resistant and delivers in vivo antitumor efficacy" presented by Melanie Frigault, Ph.D., Vice President of Translational Medicine, Vincerx, include:

A 10-fold range of sensitivity to VIP152 was observed in cisplatin-sensitive and cisplatin-resistance ovarian, uterus, uterus/cervix, and vulva cancer cell lines demonstrating the cytotoxic effects of VIP152.
High tumor mutation burden (TMB) is identified as a feature associated with VIP152 in the most sensitive quartile of gynecologic cell lines and will be validated in an independent cohort.
Antitumor efficacy was observed following a single 17.5 mg/kg dose of VIP152 monotherapy as demonstrated by tumor growth inhibition in the A2780 ovarian cancer xenograft model.
VIP152 treatment administered on an intermittent treatment schedule (once weekly), showed predictable pharmacokinetic properties and conferred a shift in transcriptional program, supporting an oncogenic shock mechanism of action, with significant reduction in MYC protein expression in patient-derived ovarian and endometrial cancer tissues samples as well as a downregulation of CDK9-regulated genes MYC, MCL, and PNCA mRNA expression in the blood of patients with gynecologic cancer.
Four out of seven patients with gynecologic cancers treated with VIP152 had stable disease, including all 3 of the MYC-amplified patients, at their first assessment. One patient remains on treatment. Although duration on monotherapy treatment is short, we believe this is a signal that warrants further exploration including in combination studies.
Neutropenia is an on-target (CDK9) toxicity via downregulation of MCL1 and is monitorable and manageable with supportive care. Once weekly dosing of VIP152 allows for recovery of neutrophils before the next dose.
Data support the ongoing Phase 1 clinical trial of VIP152 (ClinicalTrials.gov Identifier: NCT02635672).
The poster can be accessed on the presentations section of the Vincerx website.

On April 8, 2022 Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a clinical-stage company developing targeted immunotherapeutic drugs, reported that data from preclinical studies of the company’s proprietary Fully-Human Albumin Binding candidates, SON-1010, SON-1210, and SON-1410, will be presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, April 8-13, in New Orleans, Louisiana (Press release, Sonnet BioTherapeutics, APR 8, 2022, View Source [SID1234611692]).

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"We are excited about these data that support tumor growth reduction following administration of both SON-1210 and SON-1410 in a B16-F10 melanoma model in mice," said John Cini, Ph.D. Chief Scientific Officer and Co-Founder of Sonnet BioTherapeutics. "Specifically, these new data elucidate the potential for transitioning tumors from being immunologically "cold" to clinically responsive and "hot". We look forward to dosing the first patient in the forthcoming clinical trial with our SON-1010 compound, an event that will set the table for our continued development of the SON-1210 and SON-1410 bispecific candidates."

Full data are available in the abstract titled, "An Innovative Human Platform for Targeted Delivery of Bispecific Interleukins to Tumors" and the accompanying poster, the top line highlights from which are as follows:

Interleukins-12, -15, and -18 are among the most potent inducers of anti-tumor activity in animal models and have been evaluated in numerous clinical studies.
Sonnet’s bispecific drug candidates are constructed with IL-12 on the FHAB platform (SON-1010) and include IL12-FHAB-IL15 (SON-1210) and IL18- FHAB-IL12 (SON-1410).
A "cold" immunosuppressive B16-F10 melanoma tumor model was used for comparing the efficacy of the bispecific candidates administered in a single intravenous (i.v.) dose.
Dosing with either construct resulted in statistically significant tumor size reduction compared to placebo or native interleukin at a 5µg dose: 67% for IL12-FHAB-IL15 and 76% for IL18-FHAB-IL12.
Optimal synergistic efficacy occurred with the IL18-FHAB-IL12 bispecific.
These studies demonstrate that beyond the powerful anti-tumor effects of IL-12 evident in the monospecific IL12-FHAB, in the bispecific format, IL-12 can synergize with other cytokines to produce superior anti-tumor activity.
The abstract is available in the AACR (Free AACR Whitepaper) Online Meeting Planner at www.aacr.org and on the Sonnet website at View Source Details of the poster presentation are as follows:

Title: An Innovative Human Platform for Targeted Delivery of Bispecific Interleukins to Tumors
Abstract Number: 4229
Session: Immunology
Presentation Type: Poster
Session Date and Time: Wednesday April 13, 2022; 9:00 AM – 12:30 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 38
Poster Board Number: 9

On April 8, 2022 Orphagen Pharmaceuticals Inc., a biotech company pioneering the screening, discovery, and development of small molecule ligands that modulate orphan or unexplored members of the nuclear receptor family, reported a late-breaking presentation of new preclinical data for OR-449 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 being held April 8-13 both virtually and in-person in New Orleans (Press release, Orphagen, APR 8, 2022, View Source [SID1234611691]). The data presented demonstrate efficacy in a preclinical model of a Leydig cell tumor (LCT) of OR-449, the company’s first-in-class small molecule antagonist to the nuclear receptor steroidogenic factor-1 (SF-1 or NR5A1) and support the continued development of OR-449 as a novel targeted therapy for the treatment of LCTs as well as adrenocortical cancer (ACC), the primary indication for which it is being developed.

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"OR-449 was strategically designed at Orphagen and is the first antagonist to SF-1 to be taken into development – potent and orally bioavailable small molecules of this class have not previously been identified," said Scott Thacher, Ph.D., CEO and Founder of Orphagen. "The data presented at AACR (Free AACR Whitepaper) 2022 demonstrate that OR-449, a potent SF-1 antagonist, has clear potential for clinical efficacy in malignant LCTs as well as ACC. There is an urgent need for new therapies for LCT and ACC, and we are focused on completing IND-enabling studies of OR-449 with the goal of filing an investigational new drug application by the end of the year."

The incidence of ACC in the U.S. is 300 patients per year, and existing therapies are very limited. LCTs represent about 3% of all testicular cancers. Testicular cancer is in turn one of the most frequently diagnosed cancers in American males between the ages of 15 and 35. Malignant LCTs, though rare, are an estimated 10% of all LCTs. They are resistant to chemotherapy and radiation, responding primarily to surgery. Median survival from diagnosis is two years for these patients.

Summary of Results

OR-449 exhibits striking anti-proliferative activity in the rat Leydig tumor cell (LCT) line R2C, inhibiting DNA synthesis by >90% at 1 mM with an estimated IC50 of 68 nM.
In cell lines lacking SF-1 expression, such as HEK293, OR-449 has no anti-proliferative activity up to 20 mM, indicating that the anti-proliferative effect on R2C is SF-1-mediated and is not due to cytotoxicity.
OR-449 inhibits R2C xenograft tumor growth in immunocompromised mice at oral doses of 3, 10, and 30 mg/kg/day, with complete inhibition at a daily dose of 30 mg/kg.
Based on an mRNA response signature first identified in R2C culture, OR-449 appears to directly engage with SF-1 in the R2C tumors.
The in vivo potency and efficacy of OR-449 in the R2C model corresponds to what we previously reported for SJ-ACC3 (Crowe et al, ENDO 2021), a pediatric ACC patient-derived tumor xenograft (PDX) model.
These results highlight that OR-449 antagonism of SF-1 is a novel targeted therapeutic approach with potential utility in the treatment of ACC and malignant LCTs. Orphagen has initiated IND-enabling studies of OR-449 with an anticipated IND-filing date at the end of 2022.

The poster (abstract #LB144) titled, "Antagonism of SF-1 as a potential targeted therapy for malignant Leydig cell tumors," will be available on the AACR (Free AACR Whitepaper) Annual Meeting 2022 website for registered attendees to view from Friday, April 8 through Wednesday, July 13. The poster will also be available via the company on request. The poster will be presented in person on Tuesday, April 12 from 9 am to 12:30 pm CT at the New Orleans Convention Center, Exhibit Halls D-H, Poster Section 27, Poster Board Number 17.

The authors acknowledge the support of the following NIH grants: R43 DK 102221, R43 CA 150540, R43 HD 068078, R43 CA 099875, R44 CA 265639.

Reference: Crowe, et al. A Novel Steroidogenic Factor-1 Antagonist, OR-449, as a Targeted Therapy for Adrenocortical Cancer. ENDO 2021: J Endocr Soc, Vol5, Supplement_1, A1010

About OR-449

OR-449 is the lead candidate identified from Orphagen’s proprietary screening technology, which has led to successful discovery of the first drug-like small molecules to several orphan nuclear receptors. OR-449 is a first-in-class, orally bioavailable small molecule antagonist to SF-1, an orphan nuclear receptor that is essential for the embryonic growth and development of adrenal and gonadal tissues. Clinical targets for SF-1 antagonism by OR-449, such as ACC and malignant LCT, are derived from these tissues and express very high levels of this novel drug target.