On November 17, 2020 LabCorp reported that Seven leading diagnostics companies and laboratory service providers have formed the Access to Comprehensive Genomic Profiling Coalition (ACGP) (Press release, LabCorp, NOV 17, 2020, View Source [SID1234571227]). The goal of the organization is to collectively advocate for appropriate broad U.S. health insurance coverage of comprehensive genomic profiling (CGP) for patients living with advanced cancer. The current members of ACGP are Exact Sciences (NASDAQ: EXAS), Foundation Medicine, Illumina (NASDAQ: ILMN), LabCorp (NYSE: LH), QIAGEN (NYSE: QGEN), Roche Diagnostics (SIX: RO, ROG: OTCQX: RHHBY), and Thermo Fisher Scientific (NYSE: TMO).

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CGP testing performed soon after a diagnosis of advanced cancer better informs medical management, including treatment decisions and patient care, which can improve clinical outcomes. In advocating for coverage of CGP, ACGP will educate health insurers and other healthcare stakeholders about the clinical utility and economic value of CGP.

CGP tests assess the genomic alterations within a patient’s cancer to help physicians make more informed decisions about personalized treatment approaches. Using next-generation sequencing (NGS) with a tissue biopsy or a blood sample, this testing method can detect the four main classes of alterations known to drive cancer growth: base substitutions, insertions and deletions, copy number alterations (CNAs), and rearrangements or fusions. These tests can reveal clinically relevant alterations and biomarkers in the tumor’s DNA and RNA. This helps identify patients who could respond to specific targeted therapies and immunotherapy that can be more effective and may have fewer side effects. Healthcare professionals can use CGP to help predict patient benefit across multiple targeted therapies and cancer indications, with benefits in progression-free survival for patients with non-small cell lung cancer (NSCLC) as one example.1

"Cancer is a disease of the genome, not solely the tissue. Tumor profiling has evolved tremendously in the last decade," said Jim Almas, MD, vice president and national medical director of clinical effectiveness at LabCorp, and the chairman of ACGP. "The manufacturers and laboratories forming the coalition have produced incredible assays to help identify the mutations driving advanced cancers, leading patients to better care through targeted cancer treatments."

Despite evidence of the benefits of this approach, some health insurers still use an outdated framework to evaluate coverage for CGP, creating a disparity in access across patient populations. Many commercial insurance plans do not cover this type of testing, while public or government plans like Medicare do. Limited insurance coverage options may prevent some treating physicians from ordering CGP for their patients.

"There is no question that obstacles to coverage have inhibited physicians from ordering comprehensive genomic profiling," said Almas. "Additionally, we believe some clinicians are not aware of the advantages of a comprehensive testing approach and the benefits of one CGP test to provide genomic profiling, detect microsatellite instability and tumor mutational burden, and help physicians identify clinical trials for which patients may be candidates."

On November 17, 2020 Immunome, Inc. (Nasdaq: IMNM), a biopharmaceutical company utilizing a proprietary human memory B cell platform to discover and develop first-in-class antibody therapeutics, with a focus on oncology and infectious diseases including COVID-19, reported third quarter 2020 financial results and recent highlights (Press release, Immunome, NOV 17, 2020, View Source [SID1234571261]).

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"The completion of our recent IPO marks a significant milestone for Immunome and positions us to further accelerate the output of new discoveries from our platform, and to rapidly advance our lead oncology and COVID-19 therapeutic antibody programs into the clinic," said Purnanand Sarma, PhD, President and CEO of Immunome. "We are on track to execute on our near-term clinical and strategic plans, including filing IND applications for two of our programs in 2021." Dr. Sarma further stated, "I am proud of the tremendous progress our team has made this year, particularly with regard to the notable effort and dedication supporting our accelerated development of antibody-based treatment targeting multiple viral antigens to treat the COVID-19 virus. As previously announced, Immunome was awarded a $13.3 million contract from the US Department of Defense to develop an antibody cocktail discovered by the interrogation of memory B cells from ‘super-responders’ to the SARS-CoV-2 virus (DoD Press Release)."

Recent Highlights

In October 2020, Immunome completed an IPO, including the full exercise of the underwriters’ option to purchase additional shares, resulting in gross proceeds of $44.9 million, before deducting underwriting commissions and offering expenses.
IMM-BCP-01: Unlike approaches solely directed at neutralizing the Spike protein by other companies, we aim to develop an antibody cocktail directed at multiple SARS-CoV-2 antigens. Unbiased interrogation of SARS-CoV-2 "super-responder" memory B cells using Immunome’s discovery engine has resulted in the following advances:
We discovered that more than 50% of the antibodies isolated from super-responders are directed at non-Spike antigens, suggesting non-Spike related antibodies may play a significant role in the effective immunological clearance of this virus.
We also identified multiple neutralizing antibodies with picomolar affinity directed at SARS-CoV-2 Spike protein.
We discovered that, in addition to affinity matured IgG antibodies, COVID-19 "super-responders" appear to mount robust affinity-matured IgA responses. IgA antibodies are naturally found at the surface of respiratory track and function to prevent initial viral infection.
IMM-ONC-01: Our further pre-clinical testing continues to demonstrate that IL-38 appears to be a novel immune checkpoint. In animal models, our inhibitory antibody demonstrates antitumor effects in IL-38 expressing tumors.
Third Quarter 2020 Financial Results:

Cash and cash equivalents: Cash and cash equivalents were $6.7 million as of September 30, 2020 compared to $2.5 million as of December 31, 2019.
IPO and net proceeds: On October 2, 2020 the Company’s common stock began trading on the Nasdaq Capital Market under the ticker (IMNM) and on October 6, 2020 the IPO closed with the Company receiving net proceeds of $41.7 million, after deducting underwriting discounts but before deducting other offering expenses. After deducting other offering costs of approximately $2.8 million, aggregate net IPO proceeds to the Company were $38.9 million.
Research and development (R&D) expenses: R&D expenses were $1.6 million for the quarter ended September 30, 2020 compared to $2.2 million for the quarter ended September 30, 2019 and $5.7 million for the nine month period ended September 30, 2020 compared to $6.4 million for the nine month period ended September 30, 2019.
General and administrative (G&A) expenses: G&A expenses were $1.2 million for the quarter ended September 30, 2020 compared to $0.5 million for the quarter ended September 30, 2019 and $2.5 million for the nine month period ended September 30, 2020 compared to $1.1 million for the nine month period ended September 30, 2019.
Net loss: Net loss attributable to common stockholders was $8.4 million or $7.52 per share for the quarter ended September 30, 2020 compared to $2.7 million or $2.50 per share for the quarter ended September 30, 2019 and $13.8 million or $12.44 per share for the nine month period ended September 30, 2020 compared to $7.5 million or $6.88 per share for the nine month period ended September 30, 2019.

On November 17, 2020 Kazia Therapeutics Limited (ASX: KZA;NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported to share a summary of new paxalisib data presented at the Society for Neuro-Oncology (SNO) Annual Meeting, which is being held virtually from 19-21 November 2020 (Press release, Kazia Therapeutics, NOV 17, 2020, View Source [SID1234571289]).

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Key Points

New interim analysis of paxalisib phase II study in glioblastoma (NCT03522298) is highly consistent with prior data
Median progression-free survival (PFS) of 8.4 months reported on this analysis (versus 5.3 months for temozolomide, the existing standard of care)
Median overall survival (OS) of 17.5 months reported (versus 12.7 months for temozolomide)
First substantial presentation of safety data at a 60mg dose shows profile very similar to prior experience, with the most common toxicities including rash, stomatitis (mouth ulcers), and hyperglycemia (high blood sugar), consistent with other PI3K and mTOR inhibitors
Phase I study in DIPG (NCT03696355) shows paediatric maximum tolerated dose (MTD) of 27 mg/m2, with safety profile and pharmacokinetics similar to adult data
Kazia CEO, Dr James Garner, commented, "this is very reassuring data from the glioblastoma study, confirming our earlier results with the data now much more mature. In studies such as this, volatility is the enemy of dependability. From the very first efficacy data we reported from this study, in November 2019, through the ASCO (Free ASCO Whitepaper) and AACR (Free AACR Whitepaper) presentations in June 2020, to today’s latest analysis, the PFS and OS figures have remained extremely stable as the study has progressed. This gives us a great deal of confidence that what we are seeing is representative and reliable."

He added, "we expect this study to conclude in the first half of calendar 2021, but it has already provided useful information to guide the development of paxalisib. We have moved into the operational phase of the GBM AGILE pivotal study, and we expect that study to now be the primary focus of our work in glioblastoma from this point forward."

The poster presentation is available for download via the Kazia website at:-

View Source

Summary of Paxalisib Data in Comparison to Temozolomide (existing standard of care)

Temozolomide[1]
(FDA-approved treatment)

Paxalisib

(interim phase II data)

Progression-Free Survival (PFS)

5.3 months

8.4 months

Overall Survival (OS)

12.7 months

17.5 months

Professor Patrick Wen, the first author on the poster, commented "as this study has matured, we have seen encouraging results that are very stable over successive analyses, and very consistent with prior clinical experience in this drug. Paxalisib is now moving into the GBM AGILE study in glioblastoma, and we expect this to provide definitive data regarding the drug’s potential use in this disease and, if successful, a basis for regulatory approval. There remains a profound need for new treatments in glioblastoma, and paxalisib has proven to be an exciting potential candidate."

Initial Data from St Jude Study of Paxalisib in DIPG and Diffuse Midline Gliomas

Dr Christopher Tinkle, lead investigator for the SJPI3K study of paxalisib in DIPG and diffuse midline glioma (NCT03696355), gave an invited oral presentation on interim results from that study.

The SJPI3K study is a first-in-paediatric study, designed to establish the safety and pharmacokinetics of paxalisib in children, and to explore potential early signals of efficacy in this patient population.

The study recruited 27 patients, ranging from 3 to 16 years of age. Four patients discontinued participation prior to receiving a first dose of paxalisib, generally due to disease progression. At the time of analysis, five patients remain on paxalisib treatment, and several patients remain in post-treatment follow-up.

The paediatric maximum tolerated dose (MTD) was determined to be 27 mg/m2. The dose-limiting toxicities (DLTs) included hyperglycaemia, oral mucositis, and rash, which are entirely consistent with the adult experience.

The pharmacokinetics of the drug, a term which describes the concentration of the drug in plasma over time, was very consistent with the adult experience. The study found no meaningful difference between administration of intact capsules and administration via opening of capsules and sprinkling of contents onto a food carrier.

The study has not at this stage shown a clear survival benefit for paxalisib in comparison to historical controls. In terms of PFS, the proportion of patients alive and progression-free at six months (PFS6) was 96%, which compares favourably to an historical control of 58%[2]. However, the authors note that PFS can be a complex endpoint to interpret in DIPG trials due to the confounding effect of incidental radiological changes associated with radiation therapy.

Dr Tinkle commented, "my colleagues and I are very pleased with the outcome of this study. We have determined an appropriate dose for future paediatric work, established an acceptable tolerability profile in children, and demonstrated pharmacokinetic equivalence between intact capsule and open and sprinkled administration, which are critical steps in the development of any new drug for paediatric cancer."

He added, "DIPG is an extremely treatment-resistant disease, and no drug has ever shown convincing efficacy as a monotherapy. Our view has always been that the treatment of this disease will consist in combination therapy, and we have shown that paxalisib is eminently suitable to now be evaluated alongside other agents. We look forward to discussing follow-on work that will explore these opportunities and further investigate paxalisib’s potential."

Dr Garner commented, "we are grateful to have had the opportunity to collaborate with one of the world’s leading paediatric oncology hospitals in this study. The results provide an excellent foundation for the further development of paxalisib in DIPG, and we will be excited to discuss the next phase of work with our collaborators in coming months."

Next Steps

The paxalisib phase II study remains ongoing, with final data expected in 1H CY2021. The paxalisib arm of the GBM AGILE study has moved into an operational phase, and first patient in is expected early in 1Q CY2021.

The St Jude study in DIPG remains ongoing, with final data expected during 1H CY2021.

Investor Conference Call

Kazia is pleased to invite investors to attend a conference call to discuss the results further.

The call will be held on Thursday 19 November 2020 at 12:00pm, Sydney time (AEDT), which is 5pm on Wednesday 18 November 2020 in San Francisco (PST) and 8pm on Wednesday 18 November 2020 in New York (EST).

Participants will need to pre-register for the call via the following link:

View Source

Click the ‘Register Now’ button and follow the prompts to complete pre-registration. You will then receive a calendar invite with dial in numbers, a passcode and a PIN to dial into the conference call.

On November 17, 2020 Bristol Myers Squibb reported cold water on Celgene shareholders who have been hoping to see a payout related to the merger of the two companies (Press release, BioSpace, NOV 17, 2020, View Source [SID1234571461]). This morning, the pharma giant signaled it will fail to meet a deadline related to $9 per share Contingent Value Rights (CVR) tickets, essentially killing that payment.

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When BMS and Celgene merged, CVR payouts hinged on the approval of three drugs. The first of the three CVR medicines, Celgene’s multiple sclerosis drug Zeposia (ozanimod), was approved in March. The other drugs related to the CVR are cancer treatments, ide-cel and liso-cel (lisocabtagene maraleucel). Under terms of the deal, ide-cel, an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy, must be approved by the U.S. Food and Drug Administration by March 31, 2021. The FDA accepted the Biologics License Application for ide-cel under priority review in September.

Liso-cel, though, is another matter. The deadline to meet the CVR milestone for this cancer drug is Dec. 31. BMS had a Prescription Drug User Fee Act (PDUFA) action date of Nov. 16, but COVID-19 threw a spanner into the works, pushing back the timeline for its review.

Liso-cel is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target CD19, which is a surface glycoprotein expressed during normal B-cell development and maintained following malignant transformation of B cells. BMS is seeking approval of the drug as a treatment for adults with relapsed or refractory (R/R) large B-cell lymphoma after at least two prior therapies.

The BLA is based on the safety and efficacy results from the TRANSCEND NHL 001 trial, evaluating liso-cel in 268 patients with R/R large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade lymphoma, primary mediastinal B-cell lymphoma and Grade 3B follicular lymphoma. TRANSCEND NHL 001 is the largest study of CD19-directed CAR T cells to support a BLA to date.

In its announcement this morning, BMS said the delay is due to COVID-19-related travel restrictions at the FDA. The travel restrictions prevented the FDA from conducting an inspection of a third-party manufacturing facility in Texas before the PDUFA date. Because the regulatory agency could not ensure that the manufacturing facility meets its standards, it has deferred potential approval of liso-cel until the inspection can be completed. The FDA has not provided a new anticipated date for approval, BMS said.

Samit Hirawat, chief medical officer of Global Drug Development at BMS, said the company will continue to work with the FDA to support the ongoing review of the liso-cel BLA. Hirawat said the company is "committed to bringing liso-cel to patients with relapsed or refractory large B-cell lymphoma who still have significant unmet need."

This isn’t the first delay for liso-cel that jeopardized potential approval. Earlier this year, the FDA delayed review of the BLA for liso-cel by three months, which gave it the Nov. 16 PDUFA date.

On November 17, 2020 NantHealth, Inc. (NASDAQ: NH), a provider of enterprise solutions that help businesses transform complex data into actionable insights, reported the publication of a study that revealed RNA sequencing is not only viable but may also provide significant clinical value in analyzing a cancer patient’s specific disease biology to enable an optimized treatment decision with a higher likelihood of success (Press release, NantHealth, NOV 17, 2020, View Source [SID1234571228]). The study was published in Nature’s Scientific Reports, an open access, peer-reviewed journal dedicated to original research from across all areas of the natural and clinical sciences.

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Prepared in collaboration with NantOmics, LLC and ImmunityBio, Inc., the study was designed to explore the potential use of formalin-fixed paraffin-embedded (FFPE)-derived RNA transcriptome profiling for clinical decision-making. This technique was previously not considered to yield significant clinical value due to the lower quality, degraded samples typically produced by the formalin fixation process. FFPE is the most common method used in clinical settings for storing tumor biopsies.

The study revealed an overall sequencing success rate of 81% with highly consistent coverage in direct FFPE and fresh-frozen (FF) replicates (98% agreement). The results provide strong rationale for the use of FFPE-derived RNA sequencing in clinical decision-making based on the reproducibility, robustness, and consistency of whole transcriptome profiling. This research enables the comparison of clinical samples to research studies, which generally differ in both data collection and sequencing methods, and which may unlock highly valuable insights that would not be possible with DNA sequencing techniques alone.

"This is an important step to advancing towards molecularly informed medicine, both from the perspective of diagnostics to precise therapeutic intervention," said Dr. Patrick Soon-Shiong, CEO of NantHealth, NantOmics and ImmunityBio. "Genomic reporting capabilities could be enhanced through clinical applications resulting from this technology, including identifying cancers of unknown primary (CUP), prevalence of immune cell infiltrates in the tumor microenvironment (immunome), and expression analysis of checkpoint markers including those targeted by commercial and investigational immunotherapies," he continued.

The study also demonstrates that RNA sequencing is not only clinically viable but valuable and can provide a more thorough understanding of what genes are driving each individual patient’s tumor to better inform personalized treatment decisions.

To achieve this, researchers performed ribo-deplete RNA extractions on more than 3,200 FFPE slide samples to measure the expression of clinically significant genes that help identify treatments with the highest likelihood of response. The study included a comprehensive evaluation of RNA extraction methods (Poly-A and ribo-depletion) by comparing transcriptomes from The Cancer Genome Atlas (TCGA) cohort and 3,116 FFPE samples. Findings showed minimal differences between the two approaches within clinically important genes, while establishing a computational framework for comparing the expression of FFPE clinical samples to the growing database of research samples generated by academic studies.

"These are very exciting results from a robust scientific study of a high caliber," said Shahrooz Rabizadeh, Ph.D., Chief Scientific Officer, ImmunityBio. "The implication of using RNA sequencing to molecularly define a patient’s cancer, identify the origin of cancers of unknown primary, and most importantly, optimize treatment plans for the highest chance of success, especially with immunotherapies, is profound."

"Through this research, we demonstrated the robustness of the RNA assay and the informatics techniques that help clinicians understand the transcriptional drivers of disease in their patients, allowing the further advancement of personalized medicine," said Dr. Sandeep "Bobby" Reddy, Chief Medical Officer, NantHealth. "NantHealth knows that high-quality data is the backbone of modern medicine. This study unlocks valuable insights through a method that allows the analysis of both academic research and clinical data for treatment optimization, further strengthening our fight against cancer."

Receiving widespread attention in policy documents and the media, Scientific Reports is the seventh most-cited journal in the world, with more than 350,000 citations. The publication has an extensive network of expert peer reviewers and an editorial team who provide rigorous and objective review. Scientific Reports is guided by the same ethical and editorial guidelines as other Nature Research publications to ensure that all the research is original, scientifically robust and of the highest quality. The journal is published through a number of different channels, including nature.com, where it receives approximately two million monthly visitors.