On August 5, 2021 Pillar Biosciences, an innovative next-generation sequencing (NGS) solutions in-vitro diagnostics (IVD) company, reported the U.S. Food and Drug Administration (FDA) has given Premarket Approval (PMA) to its oncoReveal Dx Lung and Colon Cancer Assay, an NGS tissue-based companion diagnostic test for the qualitative detection of somatic mutations in DNA derived from non-small cell lung cancer (NSCLC) and colorectal (CRC) cancer tumors (Press release, Pillar Biosciences, AUG 5, 2021, View Source [SID1234585946]).

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The oncoReveal Dx Lung and Colon Cancer Assay PMA was based on clinically validated data, and allows for the test to be used as a companion diagnostic (CDx) for all FDA approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapies for NSCLC targeting EGFR mutations (Exon 19 In Frame Deletions and Exon 21 L858R Substitution Mutations), and KRAS wild-type tumor tissue (absence of mutations in codons 12 and 13) for metastatic colorectal cancer (mCRC) patients, guiding clinicians where targeted treatment with Erbitux (cetuximab) or Vectibix (panitumumab) is warranted. This panel is intended to be used on the Illumina MiSeq Dx instrument, Illumina’s NGS platform for in vitro diagnostic testing.

"We are committed to providing high quality and accurate IVD tests to enable better treatment decisions for cancer patients," said Gang Song, Ph.D., Founder and CEO at Pillar Biosciences. "Our FDA-approved product can be used by any lab that conducts NGS testing, making precision medicine accessible to all cancer patients."

"Increasing patient access to content on our Dx instrument fleet through partnerships such as those with Pillar Biosciences speaks to our mission to improve human health by unlocking the power of the genome," said Joydeep Goswami, Chief Strategy and Corporate Development Officer at Illumina. "We are committed to our ongoing partnership with the team at Pillar."

"We believe high quality specialty tests should be provided closest to where a patient resides, especially for a cancer patient. We look forward to accelerating our future development plans and bringing more innovative FDA-approved products to the providers and partners in the community setting," said Zhaohui Wang, Ph.D., Co-founder and Chief Scientific Officer at Pillar Biosciences.

On August 5, 2021 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported financial results for the quarter ended June 30, 2021, and provided an update on recent accomplishments and upcoming events (Press release, Syros Pharmaceuticals, AUG 5, 2021, View Source [SID1234585945]).

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"As Syros advances toward becoming a commercial-stage company, we are focused on execution across our growing portfolios in targeted hematology and selective CDK inhibition and made great strides in the second quarter," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "As announced today, we entered into an agreement with Roche to explore SY-5609 in combination with atezolizumab in colorectal cancer patients, marking the first clinical investigation of a selective CDK7 inhibitor with immunotherapy. Additionally, data from the Phase 1 dose-escalation trial of SY-5609 has been selected for an oral presentation at the ESMO (Free ESMO Whitepaper) Congress in September, at which time we plan to detail next steps for advancing the development of SY-5609 to further explore its potential as a novel targeted approach for difficult-to-treat cancers."

Dr. Simonian continued, "We also continued to progress our targeted hematology portfolio with the ongoing SELECT-MDS-1 Phase 3 trial of tamibarotene in RARA-positive higher-risk MDS patients, as well as the SELECT-AML-1 randomized Phase 2 study of tamibarotene in RARA-positive unfit AML patients and our dose confirmation study of SY-2101 in APL patients, both of which are on track to start in the second half of this year. As we advance these programs through the clinic, we are engaging more deeply with the clinical community to realize the potential of tamibarotene and SY-2101 to address high unmet needs and set new standards of care in these targeted patient populations."

Syros recently hosted a three-part key opinion leader (KOL) webinar series, reviewing both the progress and the opportunities for tamibarotene in higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) and for SY-2101 in acute promyelocytic leukemia (APL). The KOLs discussed the evolving treatment landscape as well as the unmet need in these diseases. An archived replay of each KOL event can be found on the Investors & Media section of Syros’ website www.syros.com.

UPCOMING MILESTONES

Targeted Hematology

Tamibarotene (formerly SY-1425): Oral RARa agonist

Initiate SELECT-AML-1 randomized Phase 2 trial of tamibarotene in combination with venetoclax and azacitidine in the second half of 2021 in RARA-positive newly diagnosed AML patients who are not suitable candidates for standard intensive chemotherapy.
Report initial data from SELECT-AML-1 in 2022.
SY-2101: Oral arsenic trioxide (ATO)

Initiate dose-confirmation study of SY-2101 in the second half of 2021.
Report confirmatory dose and pharmacokinetic data in the first half of 2022.
Initiate Phase 3 trial in patients with newly diagnosed APL in 2022.
Selective CDK Inhibition

SY-5609: Oral CDK7 inhibitor

Present additional dose-escalation data, including clinical activity data, in an oral presentation at the ESMO (Free ESMO Whitepaper) Congress 2021 from the ongoing Phase 1 trial of SY-5609 in patients with breast, colorectal, lung, ovarian and pancreatic cancers, as well as in patients with solid tumors of any histology harboring Rb pathway alterations.
Also at ESMO (Free ESMO Whitepaper), present new preclinical data in two poster presentations, one evaluating the antitumor and pharmacodynamic activity of intermittent dosing regimens for SY-5609 in ovarian cancer models and the other evaluating SY-5609 as a single agent and in combination with chemotherapy in KRAS-mutant models.
Initiate expansion portion of Phase 1 trial in the second half of 2021.
Gene Control Discovery Engine

Nominate next development candidate in 2022.
RECENT PIPELINE UPDATES

In a separate press release today, Syros announced that it has entered into an agreement with Roche, under which it will provide SY-5609 for a combination dosing cohort with atezolizumab in Roche’s Phase 1/1b INTRINSIC trial. The INTRINSIC trial is evaluating multiple targeted therapies or immunotherapy as single agents or in rational specified combinations in molecularly defined subsets of colorectal cancer patients. SY-5609 will be evaluated in combination with atezolizumab in patients with BRAF-mutant disease.
Syros also announced today that due to changes in the development landscape with the emergence of oral selective estrogen receptor degrader, or SERD, therapies, the company is no longer exploring SY-5609 in combination with fulvestrant in patients with CDK4/6 inhibitor-resistant HR-positive breast cancer.
Second Quarter 2021 Financial Results

Revenues were $5.2 million for the second quarter of 2021, consisting of $3.3 million in revenue recognized under Syros’ collaboration with Global Blood Therapeutics, Inc. (GBT) and $1.9 million recognized under its collaboration with Incyte Corporation (Incyte). Syros recognized $3.2 million in revenue in the second quarter of 2020, including $2.5 million under its collaboration with GBT and $0.7 million under its collaboration with Incyte.
Research and development expenses were $25.8 million for the first quarter of 2021, as compared to $14.8 million for the second quarter of 2020. This increase was primarily attributable to the advancement of Syros’ clinical programs and an increase in employee-related expenses.
General and administrative (G&A) expenses were $5.5 million for the second quarter of 2021, as compared to $5.1 million for the second quarter of 2020. This increase was primarily attributable to increased employee-related expenses.
For the second quarter of 2021, Syros reported a net loss of $22.5 million, or $0.36 per share, compared to a net loss of $17.2 million, or $0.38 per share, for the same period in 2020.
Cash and Financial Guidance

Cash, cash equivalents and marketable securities as of June 30, 2021 were $195.3 million, as compared with $174 million on December 31, 2020. This increase reflects the gross proceeds of $75.6 million that Syros received from its January 2021 public offering, partially offset by cash used to fund its operations.

Based on its current plans, Syros believes that its existing cash, cash equivalents and marketable securities will be sufficient to fund its planned operating expenses and capital expenditure requirements into 2023.

Conference Call and Webcast

Syros will host a conference call today at 8:30 a.m. ET to discuss these second quarter 2021 financial results and provide a corporate update.

To access the live conference call, please dial (866) 595-4538 (domestic) or (636) 812-6496 (international), and refer to conference ID 4156527. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the presentation.

On August 5, 2021 TransCode Therapeutics, Inc. (Nasdaq: RNAZ), a platform company solving the challenge of RNA delivery in oncology, reported that it has been awarded a Fast-Track Small Business Innovation Research (SBIR) grant from the NIH to support the clinical evaluation of TTX-MC138, TransCode’s lead therapeutic candidate for the treatment of metastatic solid tumors (Press release, TransCode Therapeutics, AUG 5, 2021, View Source [SID1234585944]). The award totals $2.3 million expected over three years.

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"We are honored that the NIH recognizes and supports our mission to overcome the obstacles of RNA delivery in oncology," said Michael Dudley, President and Chief Executive Officer of TransCode. "We believe our TTX delivery platform offers tremendous potential across a range of indications. Specifically, this SBIR grant will help fund our planned first-in-human study of our lead candidate, TTX-MC138, in patients with metastatic breast cancer. We look forward to submitting an eIND application in the first quarter of next year. This trial is designed to evaluate and demonstrate proof-of-concept for the mechanism of action for our novel delivery platform, potentially enabling TransCode to pursue a diverse pipeline of TTX-based therapeutics."

TransCode’s proprietary TTX platform leverages an iron oxide nanoparticle as a novel, image-guided system to safely and efficiently deliver oligonucleotides to their intended RNA target. TTX-MC138 targets MicoRNA-10b, believed to drive metastatic disease. The therapeutic has been validated preclinically in multiple indications and has been shown to induce durable regressions of metastatic disease in murine models of disseminated breast cancer.

On August 5, 2021 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported that it has entered into a clinical supply agreement with Roche (Press release, Syros Pharmaceuticals, AUG 5, 2021, View Source [SID1234585943]). Under the agreement, Syros will supply SY-5609, its highly selective and potent oral inhibitor of cyclin-dependent kinase 7 (CDK7), for a combination dosing cohort in Roche’s ongoing Phase 1/1b INTRINSIC trial, which is evaluating multiple targeted therapies or immunotherapy, including atezolizumab, as single agents or in rational specified combinations in molecularly defined subsets of colorectal cancer (CRC) patients.

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"We are pleased that Roche has chosen to study SY-5609 as part of its broader strategy to explore atezolizumab in combination with other targeted agents in defined colorectal cancer patient populations," said Nancy Simonian, M.D., Chief Executive Officer of Syros, "We believe SY-5609 is a potentially transformative targeted approach for difficult-to-treat cancers. Preclinical data has shown that CDK7 inhibition enhances the anti-tumor activity of PD-L1 inhibition, providing a strong rationale for combining SY-5609 and atezolizumab. Notably, this trial marks the first clinical investigation of a CDK7 inhibitor with an immunotherapy, and we look forward to working with Roche to evaluate the potential of this novel combination in patients with BRAF-mutant colorectal cancer."

Under the terms of the agreement, Roche will sponsor and conduct the Phase 1/1b study to evaluate the safety, tolerability and preliminary efficacy of the combination and will assume all costs associated with the study. In exchange for providing SY-5609, Syros will receive access to the data on SY-5609 in combination with atezolizumab. Syros retains all rights to SY-5609.

Selective CDK7 inhibition has been shown to target two fundamental processes in cancer: transcription and cell cycle control. Additionally, published peer-reviewed research has shown that CDK7 inhibition induces DNA replication stress and genome instability in preclinical cancer models, triggering immune-response signaling, which is further enhanced by the addition of immune-checkpoint blockade.1

In May 2020, Syros presented preclinical data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program demonstrating that SY-5609 inhibited tumor growth, including inducing sustained regressions at well-tolerated doses in CRC models. In preclinical studies, SY-5609 resulted in ≥ 50 percent tumor growth inhibition in 67 percent (20/30) of patient-derived xenograft models of CRC, and ≥ 90 percent tumor growth inhibition in 23 percent (7/30) of models. Deeper responses were observed more frequently in models with BRAF mutations (50 percent, 5/10) relative to wild-type models (10 percent, 1/10).

Syros is evaluating SY-5609 in an ongoing, multi-center, open-label Phase 1 dose-escalation study in patients with advanced breast, colorectal, lung, ovarian or pancreatic cancers, or with solid tumors of any histology that harbor Rb pathway alterations. Initial data from the dose escalation showed proof of mechanism at tolerable doses. Syros expects to report additional dose-escalation data, including clinical activity data, at the ESMO (Free ESMO Whitepaper) Congress in September and initiate the expansion portion of the trial in the second half of 2021.

On August 5, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a dermatologic diagnostics company providing personalized genomic information to inform treatment decisions, reported data presentations on two of its skin cancer gene expression profile tests at the DEF (Dermatology Education Foundation) Essential Resource Meeting (DERM2021) NP/PA (Nurse Practitioner/Physician Assistant) CME Conference, taking place from Aug. 5-8, 2021 (Press release, Castle Biosciences, AUG 5, 2021, View Source [SID1234585942]).

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DecisionDx-Melanoma:

DecisionDx-Melanoma is Castle’s gene expression profile test that uses an individual patient’s tumor biology to predict the risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node (SLN) positivity, independent of traditional staging factors. The Company will present two posters that highlight data assessing the clinical utility of the DecisionDx-Melanoma test.

The first poster, titled "Clinical utility of the 31-gene expression profile test on the management of cutaneous melanoma by nurse practitioners and physician assistants," highlights nurse practitioners’ and physician assistants’ (NP/PAs) attitudes toward the clinical use of DecisionDx-Melanoma in patients diagnosed with cutaneous melanoma.

Study methods and findings:

In 2020, an institutional review board (IRB)-approved, 20-question study was conducted to understand the perception and clinical use of DecisionDx-Melanoma by clinicians, including NP/PAs.
Of the 711 survey respondents, 266 self-identified as NP/PAs, with 50% of those (n=133) reporting ordering DecisionDx-Melanoma within the previous year.
89% of the NP/PAs responded that comprehensive prognostic testing (including DecisionDx-Melanoma) could improve patient care.
Most NP/PAs who use DecisionDx-Melanoma (97%) would recommend additional prognostic testing to close friends or family members compared to just 58% of those who do not use DecisionDx-Melanoma.
Among the NP/PAs who ordered DecisionDx-Melanoma in the previous year:
99% would recommend the test to a colleague.
Most would consider patient management changes for patients with a T1 tumor (82%) or stage I melanoma (81%) who received a high-risk Class 2B DecisionDx-Melanoma test result.
The second poster is entitled "Integration of the continuous 31-gene expression profile score and clinicopathologic features to predict sentinel lymph node status in patients with cutaneous melanoma: Use of artificial intelligence to attain near perfect prediction." The study highlights the use of artificial intelligence to combine patients’ clinical and pathological information with DecisionDx-Melanoma to improve the precision of sentinel lymph node (SLN) positivity prediction.

Study methods and findings:

An integrated DecisionDx-Melanoma test result (i31-GEP) was developed to integrate DecisionDx-Melanoma’s output, a risk assignment based on gene expression profile analysis, with clinicopathologic risk factors.
The DecisionDx-Melanoma test result was the most important variable in predicting SLN positivity in relation to the other included variables.
The independent validation phase showed that the i31-GEP provides a highly concordant prediction of SLN positivity rate compared to observed rates (linear regression slope of 0.999, with 1.0 representing complete concordance).
Of patients originally classified with 5-10% SLN positivity risk by current guidelines, DecisionDx-Melanoma reclassified 63% of those patients, whose actual risk of SLN positivity was less than 5% or greater than 10%.
i31-GEP had a high negative predictive value of 98% in patients with T1-T4 tumors.
DecisionDx-SCC:

DecisionDx-SCC is Castle’s prognostic gene expression profile test for patients diagnosed with high-risk cutaneous squamous cell carcinoma (SCC), designed to use a patient’s tumor biology to predict individual risk of metastasis for patients with SCC and one or more risk factors. Two posters highlight data assessing the clinical utility of the DecisionDx-SCC test.

The first poster, titled "Real-world clinical usage data demonstrates appropriate utilization of the prognostic 40-gene expression profile test for cutaneous squamous cell carcinoma with one or more risk factors," highlights the importance of utilizing DecisionDx-SCC test results in clinical assessments with traditional clinicopathologic risk factors for improved stratification of high-risk SCC patients.

Study methods and findings:

The objective of the study was to demonstrate the independent prognostic value of DecisionDx-SCC within existing risk assessment methods and report on the early clinical usage of DecisionDx-SCC.
Summary metrics were generated on the first 1000 samples received for DecisionDx-SCC testing that met clinical testing criteria. Metrics on early clinical usage include:
The technical reliability of DecisionDx-SCC was 96.3%.
69.0% of samples received DecisionDx-SCC Class 1 results, 26.0% received DecisionDx-SCC Class 2A results and 1.3% received DecisionDx-SCC Class 2B results.
52% of tested patients had three or more risk factors.
This study demonstrated that the intended use population (high-risk SCC patients with one or more risk factors) aligns with the cases that were submitted for clinical testing.
The study also found that DecisionDx-SCC results can be applied as an adjunct to enhance SCC risk stratification and contribute to risk-appropriate surveillance and treatment decisions.
The second poster is entitled "Clinical utility of the 40-gene expression profile (40-GEP) for improved patient management decisions when combined with current clinicopathological risk factors for cutaneous squamous cell carcinoma (cSCC): Case Series." The study highlights the significance of integrating novel molecular prognostication with traditional clinicopathological risk factors to inform selection of risk-appropriate treatment and surveillance strategies for high-risk SCC patients through two specific case reports.

Study methods and findings:

Case #1 and Case #2 were identically staged using two formal staging systems; both were male immunocompromised patients, with similarly sized, poorly differentiated tumors located on the left temple where Mohs surgery was completed.
Case #1 declined further treatment and was recurrence free. A retrospective analysis of the initial biopsy with DecisionDx-SCC highlighted a biologically less aggressive tumor (Class 1).
Case #2 presented with metastatic SCC 3 months after Mohs surgery and later died from SCC. A retrospective analysis of the initial biopsy with DecisionDx-SCC highlighted a biologically aggressive tumor (Class 2B).
These findings demonstrate the utility of the 40-GEP test as an adjunct to enhance cSCC risk stratification.
About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. To predict likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithm, i31-GEP, to produce an integrated test result. i31-GEP is an artificial intelligence-based neural network algorithm (independently validated in a cohort of 1,674 prospective, consecutively tested patients with T1-T4 cutaneous melanoma) that integrates the DecisionDx-Melanoma test result with the patient’s traditional clinicopathologic features. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Through March 31, 2021, DecisionDx-Melanoma has been ordered more than 73,396 times for use in patients with cutaneous melanoma.

More information about the test and disease can be found at www.CastleTestInfo.com.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), 2A (moderate) or 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

More information about the test and disease can be found at www.CastleTestInfo.com.