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.

On April 8, 2022 OncoMyx Therapeutics, a privately-held oncolytic virus immunotherapy company, reported the presentation of new preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 being held April 8-13 (Press release, OncoMyx Therapeutics, APR 8, 2022, View Source [SID1234611689]). The data presented at AACR (Free AACR Whitepaper) 2022 demonstrate that OncoMyx’s myxoma virus multi-armed with IL-12 and decorin infects and kills human multiple myeloma cells in vitro and demonstrates dose responsive efficacy after intravenous (IV) administration in a mouse model of multiple myeloma.

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"These data demonstrate that OncoMyx’s multi-armed myxoma virus works via direct oncolytic activity as well as immunomodulation of both the innate and adaptive immune response, including T cells and natural killer (NK) cells," said Leslie L. Sharp, Ph.D., chief scientific officer of OncoMyx. "As we look toward the clinic, we have generated a substantial amount of data on the safety and efficacy of our multi-armed myxoma virus and look forward to moving into GMP manufacturing and IND-enabling activities."

"OncoMyx’s myxoma virus is the first large, multi-armed oncolytic virus to demonstrate efficacy in preclinical models of multiple myeloma," said Steve Potts, Ph.D., MBA, cofounder and CEO of OncoMyx. "We continue to demonstrate the differentiated efficacy and immunomodulatory properties of OncoMyx’s multi-armed myxoma virus and its potential to be effective across a broad range of cancers, from hematological malignancies to solid tumors."

Substantial published research demonstrates that the myxoma virus naturally and selectively replicates in human tumor cells, infects and kills multiple myeloma cells, and stimulates the immune system. Furthermore, the large size of the myxoma genome allows for the insertion of multiple genes to arm the virus with immune modulators that can orchestrate the cancer-immunity cycle for optimal viral-mediated cancer-killing activity. OncoMyx has multi-armed myxoma virus to carry IL-12, an immune modulator, and decorin, which can affect tumor cell intrinsic signaling and microenvironment modulation.

The poster (abstract #5618) titled, "Multi-armed myxoma virus has therapeutic potential for treatment of multiple myeloma," 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 on OncoMyx’s website.

​​About OncoMyx’s Myxoma Immunotherapy Platform

OncoMyx’s multi-armed myxoma virus delivers multiple antitumor immunomodulatory proteins that target critical points in the cancer immunity cycle to modulate the tumor microenvironment and stimulate a robust anti-tumor response. Myxoma is a natural oncolytic virus, selectively infecting and killing a wide range of cancer cell types. It is also inherently highly immuno-interactive, and as a large dsDNA poxvirus, can be engineered to express multiple payloads to treat cancer. Because myxoma is not pathogenic to humans, there is no pre-existing immunity, making it highly amenable to intravenous and repeat dosing.

On April 8, 2022 Primmune Therapeutics, a biotech company harnessing the power of the innate immune system to treat solid tumors in the advanced cancer setting and for the clearance of human papillomavirus and related pre-cancerous cervical lesions, reported the presentation of interim data from a first-in-human, Phase 1 study evaluating PRTX007, a novel, small molecule toll-like receptor 7 (TLR7)-specific agonist, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans (Press release, Primmune Therapeutics, APR 8, 2022, View Source [SID1234611687]). The study is a single-center, prospective, randomized, double-blind, placebo-controlled study with 9 single-ascending dose (SAD) cohorts and 4 multiple-ascending dose (MAD) cohorts where PRTX007 is administered orally to adult healthy volunteers. In addition to assessing the safety, tolerability and pharmacokinetics of PRTX007, the study is designed to evaluate pharmacodynamic responses relevant to dose selection for patients with cancer.

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"These data from our ongoing first-in-human trial indicate that Primmune’s lead candidate, PRTX007, is well-tolerated in healthy volunteers and activates the desired components of innate and downstream adaptive immune responses while avoiding induction of proinflammatory cytokines," said James Appleman, Ph.D., Co-Founder and Chief Scientific Officer at Primmune Therapeutics. "We look forward to the clinical advancement of PRTX007 for the treatment of solid tumors in combination with checkpoint inhibitors and as a monotherapy for the treatment of human papillomavirus-driven pre-cancerous cervical lesions and the underlying infection."

Data show that PRTX007 was well-tolerated and expressed a favorable safety profile in the analyzed patient cohorts, with most adverse events (AEs) considered incidental and no instances of moderate, severe or serious AEs. In addition, every other day (QOD) dosing demonstrated stable systemic immune induction without evidence of counter-regulation. Both the clinical characteristics and unique pattern of immune induction by PRTX007 support its use in combination with immune checkpoint inhibitors.

Presentation Title: PRTX007, an Optimized TLR7 Agonist for Systemic Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)s: Interim Analysis of Phase I Study in Healthy Volunteers Presenting Author: Curtis Scribner, M.D., Chief Medical
Presenting Author: Curtis Scribner, M.D., Chief Medical Officer, Primmune
Abstract Number: 1865
Poster Number: CT189
Poster Board Number: 14
Poster Session: Phase I Clinical Trials 2 Session
Session Date and Time: Tuesday, April 12, 9 a.m. to 12:30 p.m. CT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 33

Additional highlights from the poster presentation include:

Most AEs were incidental and not dose related. The most common drug-related AE was headache, seen across both treated and placebo groups independent of dose.
At the interim analysis, PRTX007 demonstrated a favorable safety profile when administered orally to all 9 SAD and 3 MAD cohorts tested.
PRTX007 demonstrated induction of interferon-stimulated genes (ISGs) without significant increases in circulating interferons (IFNs). There was no increase in expression or circulating levels of proinflammatory cytokines (e.g., TNFα, IL-6, IL-1β)
About PRTX007

PRTX007, Primmune’s lead clinical development candidate, is designed to provide well-tolerated, controlled, long-term stimulation of the innate immune response while also potentiating long-term effective innate and adaptive immune responses. PRTX007 uniquely activates plasmacytoid dendritic cells (pDCs), leading to a systemic immune poly-IFN response without stimulating production of NF-κB-driven proinflammatory factors like IL-6, TNFα or IL-1β. Furthermore, activated pDCs directly deliver interferons to target cells by paracrine transfer. This is functionally equivalent to administering a cocktail of all Type I/III IFN while avoiding the associated side effects and adverse events. PRTX007 is being rapidly advanced towards clinical trials for solid tumors in the advanced cancer setting and for clearing human papillomavirus-driven pre-cancerous cervical lesions.