On September 12, 2022 Cardiff Oncology, Inc. ( Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported plans to conduct a randomized Phase 2 trial of onvansertib in combination with standard-of-care (SoC) FOLFIRI/bevacizumab in second-line RAS-mutated mCRC, durability of responses from its ongoing Phase 1b/2 clinical trial in KRAS-mutated mCRC and additional business updates (Press release, Cardiff Oncology, SEP 12, 2022, View Source [SID1234619465]).

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"We designed our next clinical program in mCRC, a randomized Phase 2 trial we have named ONSEMBLE, to accelerate and de-risk our lead indication," said Mark Erlander, PhD, chief executive officer of Cardiff Oncology. "Chief among ONSEMBLE’s objectives is to generate a randomized dataset to demonstrate the contribution of onvansertib over standard-of-care alone, validating the Phase 1b/2 trial results. These results show patients with different KRAS mutations experiencing durable responses to treatment with onvansertib plus standard-of-care, with an objective response rate and median progression-free survival that are well above historical benchmarks. In line with the FDA’s Project Optimus initiative, the ONSEMBLE trial will also seek to confirm the optimal dose of onvansertib in mCRC. We believe achieving these objectives could position onvansertib for a possible accelerated approval opportunity, though this would ultimately depend on the strength of the ONSEMBLE trial results."

Dr. Erlander continued, "With regards to our ongoing Phase 2 trial in pancreatic cancer, we are pleased to announce encouraging initial results that show 4 out of 5 evaluable patients achieving disease control and remaining on-treatment as of the data cutoff date. Based in part on the strength of our results in mCRC and PDAC, as well as the unmet need and market opportunity in these indications, we will be focusing our resources on these programs and will not independently fund future clinical activities in prostate cancer. We will also continue to explore onvansertib’s potential in additional indications by leveraging investigator-initiated studies, which will allow us to operate with capital efficiency. Based on this approach and our current projections, we expect our current cash resources to fund company operations into 2025."

mCRC Program: Topline data from ONSEMBLE, an open-label, randomized Phase 2 trial, expected in 2H 2024
Cardiff Oncology’s next trial in mCRC, ONSEMBLE, is designed to evaluate the safety and efficacy of onvansertib in combination with SoC FOLFIRI/bevacizumab in patients with second-line KRAS/NRAS-mutated mCRC. The trial is expected to enroll approximately 150 patients who will be randomized 1:1:1 to receive SoC alone, SoC plus 20 mg onvansertib, or SoC plus 30 mg onvansertib, with onvansertib administered on days 1-5 and 15-19 of 28-day treatment cycles. The primary endpoint of the trial is objective response rate (ORR). Progression-free survival (PFS) and duration of response (DoR) will be key secondary endpoints. Activation of the trial is expected in Q4 2022, with topline data expected in 2H 2024. If positive, Cardiff Oncology believes the trial results may position onvansertib for a possible accelerated approval opportunity in second-line KRAS/NRAS-mutated mCRC.

mCRC Program: Phase 1b/2 data presented at the ESMO (Free ESMO Whitepaper) Congress 2022 show durable responses to treatment
Data from the ongoing Phase 1b/2 trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC show patients experiencing durable responses to treatment, with a median duration of response of 11.7 months (95% confidence interval (CI): 8.9 – not reached). The ORR across all evaluable patients in the trial (n=48) is 35%, with responses observed across multiple KRAS variants. Median PFS across all evaluable patients in the trial is 9.3 months (95% CI: 7.6 – 13.5). Historical control trials of different drug combinations, including the SOC of FOLFIRI with bevacizumab, in similar patient populations have shown ORR and mPFS of 5 – 13% and approximately 4.5 – 5.7 months, respectively1-4. These data were recently featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022.

mCRC Program: Analysis from Phase 1b/2 trial shows improved ORR and mPFS in bevacizumab naïve patients
A new subgroup analysis from the ongoing Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC show an ORR of 69% and median PFS of 13.5 months in bevacizumab naïve patients (n=13). The ORR and mPFS for bevacizumab naïve patients were greater than those for the subgroup of trial participants with prior bevacizumab exposure (ORR=23%, mPFS=7.8 months, n=35), and for the population of all evaluable trial participants (ORR=35%, mPFS=9.3 months, n=48). This is well above historical control trials in mCRC which show an ORR of approximately 25% and a mPFS of approximately 6.9 months in bevacizumab naïve patients4-9. The observed increase in ORR in bevacizumab naïve patients was seen consistently across all patient characteristics and demographics in the trial. Based on these findings, the Company plans to stratify for prior bevacizumab exposure within the randomization of the ONSEMBLE trial and conduct preclinical studies to explore the apparent synergy between onvansertib and bevacizumab.

Metastatic PDAC Program: 1 partial response, 3 stable disease achieved in 5 evaluable patients
Preliminary data from 5 evaluable patients in an ongoing open-label Phase 2 trial of onvansertib in combination with nanoliposomal irinotecan and 5-FU in second-line metastatic PDAC show 1 patient achieving an initial partial response (PR) and 3 patients achieving stable disease (SD). The 4 patients achieving SD or a PR remain on study. The fifth evaluable patient discontinued the study due to progressive disease and an additional 3 patients are on-study and awaiting their first post-baseline scan as of the data cutoff date. Based on prior clinical studies, the historical ORR and median PFS for second-line PDAC patients are 7.7% and 3.1 months, respectively10,11. Additional data from the ongoing Phase 2 trial are expected in Q2 or Q3 2023.

Prostate Cancer Program
Following a strategic review of its clinical data in metastatic castrate-resistant prostate cancer (mCRPC), as well as the current and projected therapeutic landscape in this indication, the Company has decided it will not independently fund any future clinical activities in mCRPC.

Investigator-initiated Trials in Triple Negative Breast Cancer (TNBC) and Small Cell Lung Cancer (SCLC)
A single-arm, Phase 1b/2 trial of onvansertib in combination with paclitaxel in patients with unresectable locally advanced or metastatic TNBC is open for enrollment at Dana Farber Cancer Institute (DFCI). In Phase 1b, approximately 14-16 patients will be treated with different doses of onvansertib in combination with a fixed dose of paclitaxel to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of onvansertib. In Phase 2, approximately 34 patients will be treated with the selected onvansertib RP2D in combination with paclitaxel. The primary endpoint of Phase 2 of the trial is ORR, with PFS included as a secondary endpoint. Preliminary data from the trial are expected in Q4 2023 or Q1 2024. For more information, please visit NCT05383196.

A single-arm, two-stage, Phase 2 trial of onvansertib monotherapy in patients with relapsed SCLC is open for enrollment at the University of Pittsburgh Medical Center (UPMC). The trial is designed to enroll 15 patients in Stage 1, with the study proceeding to Stage 2 if 2 or more Stage 1 patients achieve an objective response. Stage 2 is designed to enroll an additional 20 patients. The primary endpoint of the trial is ORR, while key secondary endpoints include PFS and overall survival. Preliminary data from the trial are expected in Q2 or Q3 2023. For more information, please visit NCT05450965.

Webcast and Conference Call
Cardiff Oncology will host a webcast and conference call to discuss its clinical data, business updates, and corporate strategy today at 4:30 PM ET. To access the call, please dial 1-877-407-9208 (domestic) or 1-201-493-6784 (international) and refer to conference ID 13731618. The conference call will also be webcast live and a link to the webcast can be accessed here. A replay of the webcast will be available by visiting the "Events" section of the Cardiff Oncology website after its conclusion.

On September 12, 2022 Quince Therapeutics, Inc. (Nasdaq: QNCX), a biopharmaceutical company advancing innovative precision therapeutics targeting debilitating and rare diseases, reported that highlights from the company’s participation at The American Society for Bone and Mineral Research Annual Meeting (ASBMR 2022), which took place September 9 to September 12, 2022, in Austin, Texas (Press release, Quince Therapeutics, SEP 12, 2022, View Source [SID1234619464]). At ASBMR 2022, Quince presented two posters showcasing the broad applicability of the company’s highly differentiated bone-targeting platform and potential to accelerate healing directly at the site of bone injury and disease in spinal fusion and bone cancer indications.

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Stewart Low, Quince’s head of discovery, said, "Supported by more than 10 years of extensive preclinical studies, we believe Quince’s proprietary bone-targeting platform can be harnessed to enable the precise delivery of drug concentrated directly to the site of bone injury and disease to accelerate healing. We are excited to continue to bring our preclinical research forward to demonstrate the potential of our proprietary targeting platform with additional indications in spinal fusion and bone cancer as we seek to improve outcomes in underserved patient populations."

ASBMR 2022 Poster Highlights

The following are highlights from the company’s poster presentations of preclinical data exploring spinal fusion and bone cancer indications at ASBMR 2022:

Poster: Improved Spinal Fusion Through Targeted Delivery of Abaloparatide

With more than 400,000 spinal fusions performed in the U.S. every year, Quince believes there is an opportunity to utilize its bone-targeting platform to improve patient outcomes in spinal fusion with its NOV004 targeted therapeutic.
Quince developed a bone-targeting compound based on acidic oligopeptides which is designed to stimulate bone growth at spinal fusion sites.
In preclinical studies, NOV004 concentrated at spinal fusion sites to demonstrate accelerated repair in treated animals which resulted in significantly improved blinded radiographic fusion scores compared to animals treated with the current standard of care, bone morphogenic protein-2 (BMP-2).
In addition, NOV004’s subcutaneous administration would allow for repeat dosing post operatively compared to current spinal fusion strategies that generally require surgery to apply the drug and only allow for one application.
Poster: Evaluating the Efficacy of an Acidic Oligopeptide-radioisotope Chelator Conjugate to Target and Deliver Radioactive Agents to Bone Cancers

With five-year survival rates of less than 20% to 30% in patients with breast and prostate cancer related bone metastases, Quince believes there is an opportunity to utilize its bone-targeting platform to develop targeted radiotherapeutics to improve patient outcomes in breast and bone cancer related bone tumor growth.
Quince developed a radioactive acidic oligopeptide conjugate to target and deliver imaging and therapeutic agents with high tumor-bearing bone specificity.
In preclinical studies, the company confirmed that its targeting moiety can localize to metastatic tumor sites in both osteolytic and osteoblastic lesions and can selectively deliver both fluorescent dye and radioisotope-chelated agents without obvious offsite localization.
In addition to demonstrating rapid renal excretion, the radioactive conjugates were retained in the diseased bone even at two weeks post injection.
To view the posters presented at ASBMR 2022, please visit the Science section of Quince’s corporate website.

On September 12, 2022 PDC*line Pharma, a clinical stage biotech company developing a new class of potent and scalable active immunotherapies for cancers, reported the first results of PDC-LUNG-101 phase I/II clinical trial (NCT03970746) with PDC*lung01, the company’s therapeutic off-the shelf cancer vaccine candidate for Non-Small Cell Lung Cancer (NSCLC) (Press release, PDC Line Pharma, SEP 12, 2022, View Source [SID1234619463]). The preliminary data was presented today at a poster discussion session at the 2022 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting. This showed that PDC*lung01, in monotherapy and combined with pembrolizumab, evokes an acceptable safety profile, immunological activity and a promising tumour response in Non-Small Cell Lung Cancer, with the caveat of low numbers at the present time.

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The objectives of the phase I/II trial (PDC-LUNG-101) are to assess the safety, tolerability, immunogenicity and preliminary clinical activity of the drug candidate PDC*lung01, associated with, or not, anti-PD-1 treatment in NSCLC patients. PDC*lung01 is planned to be administered to 64 evaluable HLA-A*02:01 positive NSCLC patients at two dose levels in two different settings:

As a single agent to patients in the adjuvant setting (A1: Low Dose, A2: High Dose)
Or added to standard of care anti-PD-1 monotherapy to patients with first-line stage IV (metastatic) NSCLC disease with PD-L1 tumour proportion score ≥50% and no targetable driver mutation, (B1: Low Dose, B2: High Dose)
PDC*lung01 is a cell suspension of seven active agents – made of irradiated human Plasmacytoid Dendritic Cells (PDC*line), loaded with HLA-A*02:01-restricted peptides, derived from NY-ESO-1, MAGE-A3, MAGE-A4, Multi-MAGE-A, MUC1 and Survivin tumor antigens. PDC*line is a potent professional antigen-presenting cell that is able to prime and boost the patient’s antitumor cytotoxic CD8+ T-cells and is synergistic with anti-Programmed Death-1 (PD-1) treatment. It is administered weekly by a subcutaneous and intravenous route, in six consecutive doses. Clinical activity is assessed only for B cohorts. Results are reported on the first three cohorts that have been completed (A1/A2/B1).

"With preliminary clinical data now available from patients of the first three enrolled cohorts, it is encouraging to see PDC*lung01 as safe, immunogenic and to have signs of clinical efficacy. Durability of response in all first-line stage IV (metastatic) NSCLC patients with partial response or stable disease is particularly encouraging and provides hope for this patient group where there is still a significant unmet need. I look forward to seeing further clinical results of this compound in NSCLC patients," said Prof Vansteenkiste, head of clinic – respiratory oncology unit and trial unit – department of respiratory diseases (KU Leuven / Belgium) and chair of the Data Safety Monitoring Board for the PDC-LUNG-101 trial.

"I am very pleased that we have been able to present this encouraging data from the PDC-LUNG-101 trial, evaluating PDC*lung01 in combination with a checkpoint blockade. This is a very encouraging step for the company and we are looking forward to sharing a more mature set of data when the B2 cohort is completed," said Dr. Channa Debruyne, medical director of PDC*line Pharma.

"These new results reinforce our differentiating data package for PDC*lung01.They support the potency of our platform to trigger anti-tumour specific and effector memory T-cells against lung antigens in a large proportion of subjects, with a dose effect and a combined effect with anti-PD-1," said Eric Halioua, CEO of PDC*line Pharma.

Key highlights from the poster presentation

Poster title: Open-label, dose escalation, Phase I/II study to assess safety, tolerability, immunogenicity and preliminary clinical activity of the therapeutic cancer vaccine PDC*lung01 with or without anti-Programmed Death-1 (PD-1) treatment in patients with non-small cell lung cancer (NSCLC).

PDC*lung01 treatment was feasible with an acceptable safety profile
Of the 25 patients (6 in A1, 12 in A2 and 7 in B1) that started treatment, 22 received at least five doses and were evaluable. Treatment-related adverse events were all Grade 1-2 and one Grade 3 with no dose-limiting toxicity (DLT) observed. Six patients experienced a serious adverse event (SAE), of which only one was considered possibly related to PDC*lung01, occurring six months post-treatment
PDC*lung01 is found to be biologically active to trigger an antitumor immune response in a significant number of patients
A peptide-specific and memory CD8+ T-cell response was induced against the lung antigens of PDC*lung01 in 33%, 45% and 67% of evaluable patients in, respectively, A1, A2 and B1 cohorts
PDC*lung01 is associated with a promising Objective Response Rate and Progression Free Survival in combination with pembrolizumab in first line setting stage IV patients
The best overall response in six evaluable patients of the B1 cohort, according to RECIST criteria, included four partial responses, one stable disease and one progressive disease, leading to an objective response rate of 66.7% (80% CI 33.3% – 90.7%). Progression Free Survival at nine months for the same patient population is 66.7% (80% CI 36.4% – 85%)
The abstract is available here.

About PDC*line Pharma’s technology

PDC*line’s biological features provide unique advantages:

A professional antigen-presenting cell line, much more potent than conventional dendritic cells in priming and expanding antitumor-specific cytotoxic CD8+ T cells (conventional tumor antigens and neoantigens)
While allogeneic, PDC*line is not rejected by the host immune system; it can be injected several times to boost the immune response
Easily produced on a large scale, with a fully mastered and simple manufacturing process (via use of bioreactors with a synthetic medium without growth, differentiation or activation factors)
Easy to use: after thawing, the same off-the-shelf product is used to treat the whole target population with a cancer type expressing the target antigens
Very versatile: tumor antigens can be provided by peptide loading, mRNA transfection or retrovirus transduction of PDC*line and the target population can be extended beyond HLA-A2, (currently used as it is expressed by 50% of the Caucasian population) by using other HLAs, either already expressed by PDC*line or added by genetic modification. Moreover, within a few weeks new candidates can be validated for new cancer indications within a few weeks, with ex vivo testing using human peripheral blood mononuclear cells (PBMC)
Synergizes with anti-PD-1 to activate antitumor CD8 T cells

On September 12, 2022 CANbridge Pharmaceuticals, Inc. (HKEX:1228) , a China and U.S.-based global biopharmaceutical company committed to the research, development and commercialization of transformative therapies to treat rare diseases and oncology, reported that it will be participating in two upcoming investor conferences (Press release, CANbridge Life Sciences, SEP 12, 2022, View Source [SID1234619462]).

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Morgan Stanley 20th Annual Global Healthcare Conference (New York)
CEO, James Xue, PhD, to participate in a fireside chat on Wednesday, September 14, 2022 at 4:05 PM EST
J.P. Morgan Global Healthcare Shanghai Conference (Shanghai)
September 26- 27

On September 12, 2022 InnoCare Pharma (HKEX: 09969) reported that the Company has received Investigational New Drug (IND) approval of clinical trial from the NMPA (National Medical Products Administration) for its B-cell lymphoma-2 (BCL2) inhibitor ICP-248, which is the Company’s fifth innovative drug to enter the clinical stage in the field of hematology, and also the 13th drug entering the clinic in the pipeline (Press release, InnoCare Pharma, SEP 12, 2022, View Source [SID1234619461]).

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ICP-248 is a novel, orally bioavailable BCL2 selective inhibitor, which aims to treat non- Hodgkin’s lymphoma (NHL), acute lymphoblastic leukemia (ALL) and other malignant hematological tumors as a monotherapy or in combination with BTK inhibitors and other drugs. BCL2 is an important part of apoptotic pathway and is overexpressed in a variety of hematologic malignancies. ICP-248 has anti-tumor effects by activating the endogenous mitochondrial apoptosis pathway that causes rapid cancer cell apoptosis.

Dr. Jasmine Cui, the Co-founder, Chairwoman and CEO of InnoCare said, "ICP-248 will further strengthen our hematology pipeline. We have built multiple drugs that cover a variety of important hema-oncology targets such as BTK, CD19, CD20xCD3, BCL2 and E-3 ligase to address the unmet medical needs."