On June 1, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage immuno-oncology corporation, reported that investigators shared new positive data for its DeCidE1 (DPX-Survivac with low dose Cyclophosphamide and Epacadostat) clinical trial at the 2019 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, IMV, JUN 1, 2019, View Source [SID1234536848]).

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These new data are from the ongoing Phase 1b/2 trial evaluating the safety and efficacy of IMV’s lead candidate DPX-Survivac and intermittent low-dose cyclophosphamide (CPA), with and without Incyte’s IDO1 enzyme inhibitor epacadostat, in patients with advanced recurrent ovarian cancer. New data from evaluable patients from the phase 2 monotherapy arm of the trial indicated the potential for DPX-Survivac to impact solid tumor growth in hard to treat ovarian cancer patients. Longer-term follow-up from the phase 1b portion of the trial continued to demonstrate that the levels of survivin-specific T cells in the blood of patients – a measure of DPX-Survivac’s novel mechanism of action (MOA) – correlated with durable clinical benefits.

Updated Clinical Data for DeCidE1

In a poster presentation, Janos L. Tanyi, M.D., Ph.D., Assistant Professor of Obstetrics and Gynecology at the Hospital of the University of Pennsylvania, provided an update on the clinical results from the first patients enrolled in the phase 2 monotherapy cohort. Researchers have enrolled 19 of 28 participants to date:

Of seven patients evaluable at data cut-off in the monotherapy arm, five showed signs of treatment benefits, including reduction of target lesions in two patients, while two patients progressed.

Within the group of four patients with low tumor burden – a potential predictor of response – three showed stable diseases including two reductions in tumor burden continuing the positive trend seen in earlier results.

All subjects evaluable for T cell responses (five of five) showed survivin specific T cell activation in the blood, four of five showed a robust response. IHC analysis for tumor infiltration is ongoing

Treatments have been well tolerated.

"We believe that immunotherapy can and should be an integral part of treatment options for hard-to-treat cancers, including solid tumor indications like ovarian cancer in which patients continue to maintain an urgent need for better outcomes," said Frederic Ors, Chief Executive Officer, IMV Inc. "We continue to accumulate evidence of DPX-Survivac’s clinical activity in these patients and are encouraged by the multiple tumor shrinkages and long-lasting responses we have seen to date."

The data also highlighted long-lasting responders from the phase 1b portion of the study with key takeaways as follows:

Prolonged duration of clinical benefits reaching up to more than two years, surpassing the progression-free survival to previous treatments, including platinum-based chemotherapy.

Long-lasting clinical benefits and high levels of survivin specific T cells are associated with long-term treatment;

One subject has received DPX-Survivac for more than 21 months so far. This finding is the longest duration of treatment for DPX-Survivac on record to date.

It is supportive of DPX Survivac’s ability to maintain high levels of survivin-specific T cells in the blood over a prolonged period of time.

About the DeCidE1 Phase 1b/2 Trial

The DeCidE1 study is an open label, uncontrolled phase 1b/2 trial to assess the safety and efficacy of DPX-Survivac and cyclophosphamide with and without epacadostat in individuals with advanced, platinum-sensitive and resistant ovarian cancer. IMV completed enrollment of 53 subjects in the phase 1b cohort in December 2018. Following positive top line data, IMV amended the phase 2 protocol to stop enrollment in the combination arm with epacadostat and evaluate DPX-Survivac monotherapy with CPA in patients with lower tumor burden. As of the May 27, 2019 data cut-off date, 12 subjects have been enrolled in the phase 2 randomized portion of the trial and 7 subjects have been enrolled so far in the monotherapy population with lower baseline tumour burden.

The amended phase 2 cohort of the DECIDE1 trial is targeting enrollment of at least 16 subjects in the population with a lower baseline tumor burden. Enrollment is ongoing at multiple sites in the U.S. and Canada.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapies that programs targeted T cells in vivo. It has demonstrated the potential for industry-leading targeted, persistent, and durable T cell activation. IMV believes this mechanism of action (MOA) is key to generating durable solid tumor regressions. DPX-Survivac consists of survivin-based peptides formulated in IMV’s proprietary DPX drug delivery platform. DPX-Survivac is designed to work by eliciting a cytotoxic T cell immune response against cancer cells presenting survivin peptides on their surface.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to anti-cancer therapies. IMV has identified over 15 cancer indications in which the over-expression of survivin can be targeted by DPX-Survivac.

DPX-Survivac has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer, as well as orphan drug designation status from the U.S. FDA and the European Medicines Agency (EMA) in the ovarian cancer indication. It is currently being evaluated in multiple Phase 1b/2 clinical trials.

On June 1, 2019 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported updated safety and activity data for BPX-601 from a Phase1/2 study in patients with metastatic pancreatic cancer expressing prostate stem cell antigen (PSCA) (Press release, Bellicum Pharmaceuticals, JUN 1, 2019, View Source [SID1234536746]). The most recent cohort of patients enrolled incorporated a standard lymphodepletion conditioning regimen consisting of fludarabine/cyclophosphamide (Flu/Cy) prior to receiving BPX-601 GoCAR-T cells. Updated data from this study—including patients from this Flu/Cy cohort—will be presented during the 2019 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 1, 2019.

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BPX-601, the company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC, inducible MyD88/CD40 via administration of rimiducid, is designed to provide a powerful boost to T cell proliferation and persistence and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta.

"These updated results in patients with advanced pancreatic cancer showed that more intense lymphodepletion with Flu/Cy resulted in increased BPX-601 CAR-T cell expansion and prolonged persistence in patients treated with single-dose rimiducid," said Carlos R. Becerra, M.D., lead study investigator, oncologist, and medical director of the Innovative Clinical Trials Center at Baylor University Medical Center at Dallas. "Evidence of biological activity and stable disease was observed in this ongoing trial in these heavily pretreated patients who desperately need additional treatment options. We consider these results highly encouraging."

"I am excited that additional data from our BPX-601 trial continue to support the potential of our GoCAR-T technology platform. Our data presentation at ASCO (Free ASCO Whitepaper) supports the safety and early clinical activity of BPX-601, and provides further evidence of the impact of our technology in driving the expansion and persistence of T cells in patients," said Rick Fair, President and CEO of Bellicum Pharmaceuticals. "We have initiated the next step in the study to enroll an additional cohort to evaluate repeat rimiducid dosing to re-activate iMC over time, which is intended to deepen and extend the treatment effect. Initial results from this cohort are expected in late 2019."

Study Overview and Results

This Phase 1/2 trial has been designed to enroll patients with PSCA-positive pancreatic cancer to assess the safety, biologic and clinical activity of BPX-601. As of April 23, 2019, the data cut-off date for the current analysis, 18 patients have been treated with BPX-601. The initial 13 patients received BPX-601 following Cy lymphodepletion, and 5 patients in the latest cohort received BPX-601 following Flu/Cy lymphodepletion. Four patients did not receive rimiducid, and 14 patients received a single dose of rimiducid approximately one week following BPX-601. Following is a summary of the results to date:

Peak Vector Copy Number (VCN) of T cells was enhanced by the administration of rimiducid to activate iMC, increasing cell dose, and lymphodepletion with Flu/Cy Rimiducid-dependent increase in serum cytokines and chemokines observed in most patients, particularly those in the Flu/Cy cohort T cell persistence of >3 weeks was observed in nine of 17 patients (53%) with a minimum of 28 days of follow-up samples, including all 5 patients (100%) who received Flu/Cy Administration of BPX-601 followed by single-dose rimiducid was well tolerated with no dose-limiting toxicities Adverse Events (AEs) were generally consistent with those experienced by advanced cancer patients undergoing cytotoxic chemotherapy and other cancer immunotherapies
All 18 patients treated with BPX-601 reported at least 1 AE. The most frequent AEs regardless of causality were febrile neutropenia (33%), fatigue (28%), neutropenia (28%), pyrexia (28%), dysuria (22%), hematuria (22%) and nausea (22%).
The majority of AEs related to BPX-601/rimiducid were mild to moderate in intensity and resolved with or without supportive care. New treatment related adverse events in the Flu/Cy cohort included:
One patient experienced Grade 2 cytokine release syndrome (CRS) post-rimiducid infusion, received treatment with a single infusion of IV tocilizumab, and the event resolved the same day One patient experienced Grade 2 encephalopathy post-rimiducid infusion with no concomitant CRS. Symptoms resolved with corticosteroids within 1 week Four patients experienced Grade 1-3 urologic toxicity (dysuria, hematuria, cystitis). Symptoms in all patients resolved with standard supportive care (analgesics, anticholinergics, bladder irrigation)
Of 13 efficacy-evaluable patients treated with BPX-601 and a single dose of rimiducid, 8 patients (62%) had stable disease, and 3 patients had tumor shrinkage of 10% to 24% With median duration of follow-up of 9.1 weeks (range: 2.9 – 30.3 weeks), the median time to follow-on cancer therapy in patients who received subsequent therapy was 16.6 weeks (range: 5.6 – 30.3 weeks) In the Flu/Cy cohort, 2 patients with at least the median follow-up of 9.1 weeks had a time to next treatment of >22 weeks which was ongoing at the time of the data cutoff
The poster, titled Ligand-Inducible, Prostate Stem Cell Antigen (PSCA)-Directed GoCAR-T Cells in Advanced Solid Tumors: Preliminary Results with Cyclophosphamide (Cy) ± Fludarabine (Flu) Lymphodepletion (LD), may be found on the Bellicum website under Abstracts and Presentations.

About BPX-601

BPX-601, the company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for solid tumors expressing prostate stem cell antigen (PSCA), including pancreatic, gastric, and prostate cancers.

On June 1, 2019 Replimune Group, Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported that the Phase 2 portion of the Company’s Phase 1/2 clinical trial of RP1 alone and in combination with nivolumab anti-PD1 therapy has initiated (Press release, Replimune, JUN 1, 2019, View Source [SID1234536762]). In the Phase 2 portion of the clinical trial, RP1 in combination with nivolumab will be tested in four 30-patient cohorts of patients with melanoma, non-melanoma skin cancers (NMSC), metastatic bladder cancer or microsatellite instability-high (MSI-H) tumors. Enrollment is now open in the melanoma, NMSC and bladder cancer cohorts, and enrollment in the MSI-H cohort will open as soon as a protocol-required MSI-H patient is evaluable from Phase 1. The patients enrolled into the melanoma cohort either will be treatment naïve or have received one prior systemic therapy, and the patients enrolled into the other three cohorts will all be naïve to anti-PD1 therapy.

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Data relating to the Phase 1 portion of the clinical trial, including biomarker data, is expected to be presented at a medical conference in the fourth quarter of 2019. The Phase 1 portion tested single agent RP1 by direct injection into a single superficial or nodal tumor and by imaging guided injection into a single visceral tumor in patients with advanced heavily pre-treated cancers who failed available therapy to define the recommended Phase 2 dose. Following determination of the recommended Phase 2 dose, an expansion group of advanced cancer patients who failed available therapy then received RP1 at the recommended Phase 2 dose in combination with nivolumab at standard clinical doses.

Poster Presentation at ASCO (Free ASCO Whitepaper)
The Company also announced that a trial in progress (TiP) poster will be presented today at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting currently being held in Chicago, IL. The poster describes the design and current status of the Phase 1/2 clinical trial, including the tumor types of the patients enrolled, and will be made available on the Company’s website at the time of presentation.

Details of Replimune’s poster presentation:

Abstract Title: An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination with PD1 Blockade in Patients with Solid Tumors (Abstract TPS2671)

Session Title: Developmental Immunotherapy and Tumor Immunobiology

Session Date and Time: Saturday June 1st, 8:00am-11:00am CDT

Location: McCormick Place, Exhibit Hall A, Poster Board #301b

About RP1
RP1 is Replimune’s first Immulytic product candidate to enter the clinic and is based on a proprietary new strain of herpes simplex virus engineered to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response.

On June 1, 2019 Mersana Therapeutics, Inc. (Nasdaq: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported new interim efficacy and safety data from its ongoing Phase 1 dose-escalation study evaluating XMT-1536, its first-in-class ADC candidate targeting NaPi2b, in patients with ovarian cancer, non-small cell lung (NSCLC) adenocarcinoma and other tumor types (Press release, Mersana Therapeutics, JUN 1, 2019, View Source [SID1234536916]). The data will be presented in a poster session and poster discussion today at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held from May 31 — June 4, 2019 in Chicago, IL.

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"We are encouraged by the early signs of efficacy coupled with the favorable safety and tolerability profile and promising treatment duration we have seen to date in this ongoing Phase 1 study with XMT-1536 in heavily pre-treated, advanced cancer patients," said Anna Protopapas, President and CEO, Mersana Therapeutics. "We look forward to moving into the dose expansion phase of the study which will focus on platinum-resistant ovarian cancer and NSCLC adenocarcinoma patient populations."

In a poster titled "Phase 1 dose escalation study of XMT-1536, a novel NaPi2b-targeting antibody-drug conjugate (ADC), in patients (pts) with solid tumors likely to express NaPi2b," Mersana demonstrated that as of May 10, 2019, XMT-1536 is well tolerated at doses up to 30 mg/m2, with observation of objective responses at 20 mg/m2 and higher. Of the 37 patients enrolled, tumor types included 22 ovarian, fallopian tube or primary peritoneal cancer, four NSCLC, eight endometrial, two papillary renal, and one salivary duct cancer. Patients were heavily pre-treated, with a median of four prior lines of treatment (range 1-13) for all patients and a median of five lines of prior treatment in ovarian cancer patients (range 1-11). Interim results included:

· The most common treatment-related adverse events (TRAEs) were Grade 1-2 nausea, fatigue, and headache, and the most frequent Grade 3 TRAE was transient AST elevation.

· In patients with tumor types selected for the planned expansion phase (platinum-resistant ovarian cancer and NSCLC adenocarcinoma) treated at >20 mg/m2 (N=18), three (17%) achieved partial responses (PRs) and eight (44%) achieved stable disease (SD) for a disease control rate (DCR) of 11/18 (61%), and a treatment duration lasting beyond 16 weeks in 9 patients (50%).

· In ovarian cancer patients treated at >30 mg/m2 (N=7), two (28%) achieved partial responses (PRs) and three (43%) achieved stable disease (SDs) for a disease control rate (DCR) of 5/7 (71%), and three of these patients (43%) were treated on study for more than 16 weeks.

The Company continues to evaluate patients in the dose escalation portion of the study in the once-every-four-week dose level of 36 mg/m2. Upon completion of the 36 mg/m2 evaluation, the Company expects to choose either the 30 mg/m2 or 36 mg/m2 every four weeks as the go forward dose for the dose expansion phase of the study. Mersana is planning to begin dosing patients in the dose expansion phase in third quarter of 2019.

On June 1, 2019 Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported positive preliminary clinical data from its two first-in-human Phase 1/2 studies of SRA737, a highly selective oral Chk1 inhibitor, as monotherapy and as SRA737+LDG (SRA737 potentiated by low dose gemcitabine), at the 2019 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (Press release, Sierra Oncology, JUN 1, 2019, View Source [SID1234536764]). Anti-cancer activity was demonstrated across multiple indications and genetic contexts, with SRA737+LDG specifically achieving a notable 30% response rate in anogenital cancer patients.

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"In collaboration with Dr. Udai Banerji, Chief Investigator, The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust, we have established proof-of-concept clinical data for SRA737 and identified a potential clinical indication that could be pursued towards registration," said Dr. Nick Glover, President and CEO of Sierra Oncology. "Our strategy has been to execute a cutting-edge signal-seeking survey of a broad cancer landscape, across both a range of indications and a spectrum of genetic contexts associated with replication stress (RS). The resulting clinical data demonstrate that SRA737 has demonstrable anti-cancer activity in multiple indications, in particular in combination with LDG, and has a favorable tolerability profile, opening up several attractive development paths forward for this unique drug candidate. Of note, we have recently received management support from a major immuno-oncology company to potentially supply their leading immunotherapeutic agent to run a combination study with SRA737. We will further analyze these opportunities and evaluate next steps with this asset over the coming months, exploring options to enable the continued advancement of SRA737 in the context of our emerging pipeline."

"These clinical data provide clear evidence of anti-tumor activity with SRA737+LDG and demonstrate that the combination is well tolerated. Of particular note were the promising responses we observed in squamous cell anogenital/cervical cancers in previously treated patients with advanced disease," said Dr. Rebecca Kristeleit, Clinical Senior Lecturer and Honorary Consultant Medical Oncologist at University College London (UCL) Cancer Institute & UCLH Dept. of Oncology. "In my opinion, SRA737+LDG warrants additional registration-intent clinical development focused on patients with anogenital cancer, an indication for which the second line metastatic setting represents a significant unmet medical need with no approved therapies and very poor life expectancy."

"We are pleased that these signal-generating studies provided compelling support for our original hypothesis that SRA737’s anti-cancer activity was correlated with specific genetic contexts. Indeed, our clinical data demonstrate that anogenital cancer represents a synthesis of overlapping replication stress genetics, providing particular sensitivity to SRA737+LDG. Moreover, these findings support that low dose gemcitabine acts as an exogenous driver of RS that further potentiates SRA737’s anti-cancer activity," said Dr. Christian Hassig, Chief Scientific Officer, Sierra Oncology. "From a safety perspective, our data support that SRA737 and SRA737+LDG are conducive to development in combination with other therapeutic approaches, providing paths for further development with PARP inhibitors and with immunotherapy, combinations for which we have previously reported robust synergistic preclinical efficacy."

The company will be hosting an Analyst and Investor Event on Monday June 3, 2019, to discuss these clinical findings and potential next steps in the development strategy for SRA737+LDG. The event will feature presentations by distinguished oncologists Professor Johann de Bono and Dr. Rebecca Kristeleit.

SRA737+LDG (SRA737-02) First-in-Human Phase 1/2 Preliminary Results
This signal-seeking Phase 1/2 study (NCT02797977) was designed to investigate the safety and tolerability of SRA737 in combination with sub-therapeutic, low dose gemcitabine (LDG), as well as to evaluate preliminary anti-tumor activity of SRA737 potentiated by LDG in tumors with genetic alterations predicted to confer increased intrinsic RS and Chk1i sensitivity. Relative to standard-of-care, gemcitabine doses tested were approximately 10-25% of a standard chemotherapeutic dose.

Preliminary Efficacy Results (Evaluable Patients):

Striking anti-tumor activity was observed in subjects with advanced anogenital cancer (Overall Response Rate (ORR) = 30%; Disease Control Rate (DCR) = 60%), encompassing noteworthy tumor decreases (e.g. -66% tumor decrease; resolution of pleural effusion) and promising durations of treatment (e.g. ~11 months).
Overall, Partial Responses were observed in six subjects and 41 subjects had a best response of Stable Disease (SD); durable SD lasting ≥ 4 months was recorded in 32 subjects and was observed in all expansion cohorts.
The combination of SRA737+LDG was generally well tolerated. There was no evidence of emergent or cumulative toxicity and/or declining tolerability with up to 13 cycles of treatment. At the time of the data cut off (May 3, 2019), 22 subjects remained on study treatment.
Based on overall tolerability, the recommended Phase 2 dose is 500 mg SRA737 + 250 mg/m2 LDG.
Genetic Analyses:

Preliminary evidence suggests several intrinsic sources of RS combined with LDG significantly enhance Chk1 activity.
FA/BRCA gene network mutations were associated with the most favorable outcomes in this study (ORR = 25%; DCR = 81%). The FA/BRCA gene network encodes a series of Fanconi Anemia and other proteins involved directly or indirectly in replication fork metabolism and management of RS.
Mutations in the PI3K gene network correlated with robust DCR (75%) and tumor responses in two subjects, consistent with previous reports of Chk1i sensitivity associated with PIK3CA mutations.
A preliminary correlation of noteworthy tumor responses with elevated tumor mutational burden (TMB) was also observed, particularly in the anogenital cohort (three of four TMB patients achieved notable tumor decreases). Elevated TMB is consistent with increased genomic instability and represents a possible future enrichment strategy.
SRA737-01 Monotherapy First-in-Human Phase 1/2 Preliminary Results
This signal-seeking Phase 1/2 study (NCT02797964) was designed to investigate the safety and tolerability of continuous, oral daily dosing of SRA737, as well as to survey a broad range of cancer indications and genetic contexts in the expansion phase, in order to evaluate preliminary anti-tumor activity and delineate potential genetic signatures and/or tumor indications that might warrant additional therapeutic investigation.

Preliminary Efficacy Results (Evaluable Patients):

The maximum tolerated dose was 1000 mg per day, and based on overall tolerability and PK, the recommended monotherapy dose is 800 mg per day, highlighting the tolerability of SRA737.
Evidence of anti-tumor activity was observed in subjects with HGSOC, colorectal, prostate and non-small cell lung cancer; no RECIST PRs or CRs were confirmed, but several noteworthy tumor reductions were recorded.
HGSOC appeared as the most sensitive tumor to SRA737 monotherapy in the SRA737-01 study. Although heavily pre-treated (~5 prior lines), the HGSOC cohort demonstrated directionally favorable disease control (DCR = 54%) with notable maximal tumor reductions of 29% and 27% in two patients.
A best overall response of stable disease (SD) was seen in 34 (32%) subjects. At the time of the data cut off, durable SD lasting ≥ 4 months was recorded in 22 (21%) subjects and was observed in all Cohort Expansion phase tumor types except head and neck cancer.
Genetic Analyses:

Subjects whose tumors harbored FA/BRCA network mutations, regardless of indication, displayed favorable outcomes (DCR = 71%; DOS = 3.8 cycles), consistent with similar observations in subjects treated with SRA737+LDG.
Within the FA/BRCA pathway, several notable tumor decreases occurred in subjects harboring two genetic alterations, such as a DDR checkpoint kinase gene or within the PI3K network. This phenomenon was also observed in the SRA737+LDG clinical study.
Alterations in the PI3K gene network (PIK3CA, AKT, PTEN) were associated with a 77% DCR.
No clear trend toward enhanced sensitivity was noted with CCNE1 gene amplification, although the small subset of subjects enrolled with unambiguous CCNE1 amplifications renders definitive conclusions challenging.
The majority of subjects with notable responses (tumor reduction and/or >4 months SD) harbored alterations in either or both the PI3K and FA/BRCA gene networks. CCNE gene network alterations (DCR = 67%) partially overlapped with FA/BRCA subjects but was mutually exclusive with PI3K network alterations.
Overall, these data provide promising evidence of SRA737 anti-tumor activity and identify several gene networks associated with potentially enhanced SRA737 sensitivity.
SRA737 Analyst & Investor Event
The company will be hosting an Analyst and Investor Event on Monday, June 3, 2019, to discuss these clinical findings and potential next steps in the development strategy for SRA737+LDG.

Date and Time: June 3, 2019, 6:00 – 7:00 am CT
Location: History event room, Marriot Marquis Hotel, 2121 S Prairie Ave, Chicago, Illinois.

The event will feature presentations by two distinguished oncologists:

Professor Johann de Bono, Regius Professor of Cancer Research, Head of the Division of Clinical Studies and Professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, will discuss the critical role of Chk1 in tumor cell survival during replication stress, as well as describe potential opportunities to combine SRA737 with other therapeutic modalities including PARP inhibitors and immunotherapy agents.
Dr Rebecca Kristeleit, Clinical Senior Lecturer and Honorary Consultant Medical Oncologist at University College London (UCL) Cancer Institute & UCLH Dept. of Oncology, a leading expert in gynecological malignancies, will discuss her clinical experience with SRA737+LDG, and potential development opportunities for this novel combination in the treatment of anogenital cancers.
Event registration and webcast information are available through the Sierra Oncology website at www.sierraoncology.com. An archive of the presentation will be accessible after the event through the Sierra Oncology website.

ASCO 2019 Poster Presentations
Title: A Phase 1/2 First-in-Human Trial of Oral SRA737 (a Chk1 Inhibitor) in Subjects with Advanced Cancer.
Abstract: 3094; Poster #: 86
Poster Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)
Date and Time: Saturday, June 1, 2019, 8:00 – 11:00 am CT
Location: McCormick Place, Event room: Hall A, 2301 S King Dr, Chicago, Illinois

Title: A Phase 1/2 First-in-Human Trial of Oral SRA737 (a Chk1 inhibitor) Given in Combination with Low Dose Gemcitabine in Subjects with Advanced Cancer.
Abstract: 3095; Poster #: 87
Poster Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)
Date and Time: Saturday, June 1, 2019, 8:00 – 11:00 am CT
Location: McCormick Place, Event room: Hall A, 2301 S King Dr, Chicago, Illinois

The posters will be available on June 1, 2019 on the Sierra Oncology website at www.sierraoncology.com

About SRA737 and SRA737+LDG
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). Tumors with high levels of replication stress become reliant on Chk1 to mitigate the potentially catastrophic consequences of excess genomic instability.

Intrinsic sources of replication stress can include genetic alterations in tumor suppressors, oncogenes or DNA Damage Repair genes. Tumors harboring defects in these gene classes are hypothesized to have higher levels of intrinsic replication stress due to dysregulated cell cycle control, increased proliferation demands and increased genomic instability. SRA737+LDG is a novel drug combination, where non-cytotoxic low dose gemcitabine (LDG) acts as a potent extrinsic inducer of replication stress.

Sierra Oncology retains the global commercialization rights to SRA737.