On September 8, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported new data from its lead clinical program evaluating onvansertib in combination with standard-of-care (SOC) FOLFIRI/bevacizumab for second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Cardiff Oncology, SEP 8, 2021, View Source [SID1234587440]).

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"Our Phase 1b/2 trial continues to generate data suggesting that the addition of onvansertib to SOC results in an objective response rate and median progression-free survival that substantially exceed those previously achieved with SOC alone," said Katherine L. Ruffner, M.D., chief medical officer of Cardiff Oncology. "Radiographic responses have been observed across multiple KRAS mutation variants, which speaks to a key advantage of onvansertib over competing agents targeting individual mutations. These impressive results, which have remained consistent across both academic and community trial sites, highlight the potential for onvansertib to address the unmet need for new second-line therapeutic options to treat patients with KRAS-mutated mCRC. I look forward to the trial’s continued advancement and future data readouts."

Highlights from today’s data announcement include:

Efficacy data in patients evaluable for disease response as of data cutoff date (July 2, 2021):

Patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) across both Phase 1b and Phase 2:
8 of 19 (42%) achieved an initial partial response (PR) as of the data cutoff date
7 of 19 (37%) have achieved a confirmed PR (based on further follow-up of patients with an initial PR as of data cutoff date)
Objective response rates observed in historical control trials in similar patient populations treated with standard of care are 5-13%1-4

Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2) across both phases of the study
12 of 32 (38%) achieved an initial PR as of the data cutoff date
10 of 32 (31%) have achieved a confirmed PR (based on further follow-up of patients with an initial PR as of data cutoff date)
Median progression free survival (mPFS)

mPFS has not yet been reached in patients treated per protocol at the RP2D
mPFS across all response-evaluable patients (n = 32) is 9.4 months (95% confidence interval: 7.8 – not yet reached)
mPFS of ~4.5-5.7 months has been reported in trials used as historical controls1-4
Biomarker data as of data cutoff date across all patients:

Partial responses (PRs) were observed across different KRAS mutation variants, including the 3 most common observed in colorectal cancer (G12D, G12V, G13D)
Patients achieving a best response of PR showed the greatest decreases in plasma KRAS mutant allelic frequency (MAF) after 1 cycle (28 days) of therapy
Safety data as of data cutoff date across all patients:

The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 10% (49/490) of reported treatment-emergent adverse events (TEAEs) being G3/G4
Most reported treatment-related adverse events (TRAEs) were manageable and reversible with supportive care
Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology, commented, "The strong signal of efficacy and favorable tolerability profile observed in this trial bodes well not only for our lead mCRC program, but for each of our KRAS-focused clinical programs. The meaningful improvements we are seeing in treatment response relative to historical controls demonstrate the value of combination therapy and support the synergistic effect observed preclinically when onvansertib is added to standard-of-care irinotecan and 5-FU (FOLFIRI). We are also seeing compelling biomarker results that highlight the potential utility of plasma KRAS MAF as a predictive tool that could aid in the design of subsequent trials. Looking forward, we anticipate the ongoing Phase 2 portion of the trial to provide additional data catalysts that will advance the clinical development of onvansertib, generate value for shareholders and, most importantly, provide new treatment options for patients."

Key Opinion Leader Webinar
The newly announced data are being discussed today at 4:00 PM ET as part of a key opinion leader (KOL) webinar being hosted by Cardiff Oncology. The webinar is featuring the clinical trial principal investigator, Heinz-Josef Lenz, M.D., FACP, USC Norris Comprehensive Cancer Center, key clinical advisor Afsaneh Barzi, M.D., Ph.D., City of Hope Comprehensive Cancer Center, and members of the Cardiff Oncology management team.

To attend the webinar, click here. A replay of the webinar will be available by visiting the "Events" section of the Cardiff Oncology website shortly after its conclusion.

About the Phase 1b/2 Trial of Onvansertib in KRAS-mutated mCRC
This is a multi-center, single-arm, Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation. Patients must also have failed treatment with, or be intolerant to, FOLFOX (fluoropyrimidine and oxaliplatin) with or without bevacizumab to be eligible. The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit View Source

References

Giessen et al., Acta Oncologica 2015, 54: 187-193
Cremolini et al., Lancet Oncol 2020, 21: 497–507
Antoniotti et al., Correspondence Lancet Oncol June 2020
Bennouna et al., Lancet Oncol 2013; 14: 29–37

On September 8, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast management participation as follows (Press release, Regeneron, SEP 8, 2021, View Source [SID1234587439]):

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Morgan Stanley 19th Annual Global Healthcare Conference at 8:45 a.m. ET on Monday, September 13, 2021

Cantor Fitzgerald Virtual Global Healthcare Conference at 9:20 a.m. ET on Monday, September 27, 2021
The sessions may be accessed from the "Investors & Media" page of Regeneron’s website at View Source Replays of the webcasts will be archived on the Company’s website for at least 30 days.

On September 8, 2021 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the company will participate in the following upcoming virtual investor conferences (Press release, Jazz Pharmaceuticals, SEP 8, 2021, View Source [SID1234587438]):

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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

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BofA Virtual Global Healthcare Conference 2021 on Wednesday, September 15, 2021

The presentation will be available to registered conference attendees.
Cantor Virtual Global Healthcare Conference on Monday, September 27, 2021

The presentation is scheduled for 4:40 p.m. ET / 9:40 p.m. IST.
An audio webcast of the presentation will be available via the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. A replay of the webcast will be archived on the website for at least one week following the conference.

On September 8, 2021 HaemaLogiX Pty Ltd, a clinical stage biotech company developing novel immuno-oncology and immune therapies for patients with blood cancers, reported the close of a fully subscribed $10 million placement to sophisticated investors and welcomes Platinum Asset Management as core new institutional investor within its Platinum International Health Care Fund (Press release, HaemaLogiX, SEP 8, 2021, View Source [SID1234587437]).

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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

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Bryce Carmine, HaemaLogiX Chairman and CEO commented: "We are pleased to have secured $10 million in new capital which will enable HaemaLogiX advance the development of our lead asset KappaMab. In clinical studies to date, KappaMab has shown strong potential as an efficacy-boosting adjunct to the standard of care across multiple lines of treatment for multiple myeloma patients. Funds raised will contribute significantly to HaemaLogiX’s efforts to address the patient need in this underserved market and expedite our commercialisation efforts.

"Both new and existing shareholders have supported the raise and I’m very pleased to welcome the world-class Platinum Asset Management as a new institutional investor."

HaemaLogiX’s lead drug is a monoclonal antibody called KappaMab. It targets a cancer cell surface kappa myeloma antigen (KMA), which is believed to play a role in protecting the cancerous myeloma cell from the patient’s own immune response. When KappaMab specifically binds to the myeloma cell, it enables the patient’s immune system to recognise the cell as abnormal, triggering the natural response to attack and kill the myeloma cell.

Importantly the specificity of KappaMab has demonstrated excellent safety and efficacy in myeloma patients whose disease has relapsed. Due to its unique mode of action, KappaMab works in partnership with drugs that represent standard of care for treating multiple myeloma. These standard of care drugs have been shown to upregulate the KMA target on the myeloma cells and increase the patient’s own immune response, leading to a more effective synergistic drug combination treatment.

KappaMab’s potential to boost the efficacy of standard of care treatment has been validated by interim Phase IIb data. It is anticipated that final results of the Phase IIb clinical trial will be published in late 2021.

Placement and Use of Funds

Approximately 873k new fully paid ordinary shares in the Company (New Shares) will be issued under the Placement at the issue price of $11.60 per new share (Issue Price).

The funds raised under the placement will directly support manufacturing of the next batch of the Kappa antibody plus the conduct of a higher dose, 30mg/kg, monotherapy study and prepare for two further studies. One study demonstrating the clinical relevance of KappaMab in patients on a maintenance regime – which represents more than 50% of the overall market potential of the treatment landscape[1] – and a second study in patients who have relapsed or become refractory to other immunomodulatory drugs in previous lines of treatment.

The Company also plans to progress its antibody for lambda-type multiple myeloma (which account for 30% of multiple myeloma patients) and continue activities to secure pharmaceutical partners for technology development, which may generate income through a licence or asset sale.

On September 8, 2021 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported the Phase Ib results of the dual Bcl-2/Bcl-xL inhibitor, APG-1252 (pelcitoclax), in combination with osimertinib in patients with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) resistant non-small cell lung cancer (NSCLC), during a Mini Oral Session at the 2021 World Conference on Lung Cancer (WCLC) (Press release, Ascentage Pharma, SEP 8, 2021, View Source;mini-oral—ascentage-pharma-announces-latest-data-of-its-investigational-bcl-2bcl-xl-inhibitor-pelcitoclax-apg-1252-combined-with-osimertinib-in-patients-with-egfr-tki-resistant-non-small-cell-lung-cancer-301371959.html [SID1234587436]). The data was presented by Prof. Li Zhang, the principal investigator of the study from Sun-Yat Sen University Cancer Center.

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Organized by the International Association for the Study of Lung Cancer (IASLC), the World Conference on Lung Cancer (WCLC) is the world’s largest multidisciplinary oncology event dedicated to lung cancer and other thoracic cancers, with a focus on the most cutting-edge research and clinical advances in the field. Results presented by Ascentage Pharma at this year’s WCLC are from a single-arm, multicenter Phase Ib dose-escalation and dose-expansion study designed to evaluate the pharmacokinetics (PK), safety and preliminary efficacy of pelcitoclax in combination with osimertinib in patients with advanced EGFR-mutant NSCLC.

Being developed by Ascentage Pharma, pelcitoclax is a novel small-molecule drug candidate that restores apoptosis by selectively inhibiting Bcl-2 and Bcl-xL proteins simultaneously. In preclinical studies, pelcitoclax in combination osimertinib has demonstrated synergistic anti-tumor effects in animal models of EGFR-mutant NSCLC that were sensitive or resistant to osimertinib. Therefore, pelcitoclax in combination with osimertinib has the potential of offering a new treatment option.

Highlights of the data presented during a Mini Oral Session at this year’s WCLC:

Phase 1b Study of Pelcitoclax (APG-1252) in Combination With Osimertinib in Patients With EGFR TKI-Resistant NSCLC

Abstract: MA02.06

Track: Novel Therapeutics and Targeted Therapies

Time: 10:05 – 10:10, September 8, 2021, Mountain Time / 00:05 – 00:10, September 9, 2021, Beijing Time

This single-arm, multicenter Phase Ib study of pelcitoclax in combination with osimertinib in patients with advanced EGFR-mutant NSCLC, comprised a dose-escalation phase and a dose-expansion phase. Pelcitoclax was administered at 160 mg or 240 mg by IV infusion once a week, and osimertinib was administered orally at 80 mg daily (QD). The dose-escalation primarily evaluated the safety and tolerability of the combination regimen in patients progressed on prior EGFR TKI treatments, and determined the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of pelcitoclax. The dose-expansion comprised two arms: 1) Patients with third-generation EGFR TKI-resistant NSCLC; 2) Patients with osimertinib-naïve NSCLC. Each arm planned to enroll 20 patients.

As of June 24, 2021, 56 patients were enrolled in the study. 33 of them were enrolled in the dose-escalation and dose-expansion arm 1. Those patients had received a median of 4 (range: 1-10) lines of prior treatment, 87.9% had received chemotherapies, 75.8% had been treated with osimertinib, and 63.6% had brain metastasis at the time of enrollment. The 23 patients enrolled in arm 2 had received a median of 0 (range: 0-2) lines of prior treatment, 8.7% had received chemotherapies, 17.4% had been treated with first-generation tyrosine kinase inhibitors (TKIs), and 30.4% had brain metastasis at the time of enrollment.

In dose-escalation, 1 partial response (PR) was observed in the 11 evaluable patients. In arm 1 of the dose-expansion phase, 3 PRs (2 were osimertinib-resistant) and 13 stable diseases (SDs) were observed in the 20 evaluable patients, at an objective response rate (ORR) of 15% and a disease control rate (DCR) of 80%. In arm 2 of the dose-expansion phase, 13 PRs and 8 SDs were observed in the 22 evaluable patients, including 3 patients harboring EGFR Exon 20 insertion, at an ORR of 59.1% and a DCR of 95.5%.

In dose-escalation, one case of dose-limiting toxicity (DLT) of grade 4 thrombocytopenia was observed at 240 mg; while no grade 3 or higher thrombocytopenia was observed at 160 mg, and the increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) also occurred at much lower rate than 240 mg. Thus, pelcitoclax 160 mg per week plus osimertinib 80 mg QD was selected as the RP2D. The most common treatment-related adverse events (TRAEs) included transient thrombocytopenia, increased AST, increased ALT, increased amylase, increased blood creatinine, decreased leukocytes, anemia, and rash.

Conclusion: Pelcitoclax in combination with osimertinib was safe and well-tolerated. Preliminary synergistic anti-tumor effects were observed in some patients with osimertinib-resistant NSCLC. In patients who received osimertinib for the first time, pelcitoclax has demonstrated preliminary synergistic anti-tumor effects with osimertinib similar to that of navitoclax.
Prof. Li Zhang, the principal investigator of the study from Sun-Yat Sen University Cancer Center, said: "Although osimertinib is currently the preferred first-line treatment for patients with EGFR-mutant NSCLC, there are still no effective treatments for patients who are resistant to osimertinib. Our data presented at this year’s WCLC has demonstrated synergistic anti-tumor effects of pelcitoclax plus osimertinib in some osimertinib-resistant patients, thus indicating the potential as a new clinical strategy that could address this unmet medical need. In the next step, we will carry out additional analysis of biomarkers in an effort to enrich the patient population responding to this regimen."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented: "There is currently an enormous unmet medical need in patients with NSCLC, especially in the EGFR TKI-resistant subgroup that is in desperate need of effective treatment options. These results reported at the WCLC this year showed the therapeutic potential of pelcitoclax plus osimertinib in patients with EGFR TKI-resistant NSCLC, therefore provided rationale for the continued clinical investigations. We will press forward with this clinical development program which hopefully will offer a new treatment option to patients in need."