NextCure Raises $93 Million in Series B Financing

On November 13, 2018 NextCure Inc., a privately-held biopharmaceutical company discovering and developing the next generation of immunomedicines for cancer and other diseases, reported the completion of a $93 million series B equity financing (Press release, NextCure, NOV 13, 2018, View Source [SID1234531256]). The financing was led by Hillhouse Capital Management and Quan Capital, and included Bay City Capital, Surveyor Capital (a Citadel company), Ping An Ventures, Taiho Ventures LLC, ArrowMark Partners and NS Investment. All existing investors also participated in this financing, including Canaan Partners, Lilly Asia Ventures, OrbiMed Advisors LLC, Pfizer Inc., Sofinnova Ventures and Alexandria Venture Investments. Additionally, Eli Lilly and Company invested $15 million in this financing in conjunction with the discovery and development partnership announced on November 5, 2018.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In connection with the financing, Michael Yi, M.B.A., (Hillhouse Capital Management) and Stella Xu, Ph.D., (Quan Capital) will join the board of directors.

The proceeds will be primarily used to support clinical development for the company’s two lead drug candidates, including NC318, preclinical development of additional novel immunomedicine drug candidates, and the Company’s activities under its previously announced collaboration with Eli Lilly and Company to discover and develop novel cancer targets with the Company’s proprietary FIND-IO platform.

"We are excited to welcome a distinguished group of new investors to NextCure and appreciate the strong support from our existing investors," said Michael Richman, NextCure’s President & CEO. "We have made tremendous progress in the past 2.5 years, and look forward to the continued clinical development of NC318 and advancement of our growing portfolio of first-in-class immunomedicines."

About NC318
NC318 is a first-in-class immunomedicine against a novel immunomodulatory target found on a restricted set of myeloid cells in the tumor microenvironment and on certain tumor types including lung, ovarian and head and neck cancers. Preclinical research shows that S15 promotes the survival and differentiation of suppressive myeloid cells and negatively regulates T cell function, allowing cancer growth. In preclinical studies, NC318 blocks the negative effects of S15. NC318 is a first-in-class immunomedicine that has the potential to treat multiple cancer types.

About FIND-IO
The FIND-IO platform is designed to identify novel cell surface molecular interactions that drive functional immune responses in the tumor microenvironment and other disease sites. NextCure has developed proprietary approaches to assess immune pathways in primary immune cells and established cell lines from immune lineages, including T cells, NK cells, macrophages, myeloid-derived suppressor cells, dendritic cells, as well as cancer cells. NextCure is utilizing FIND-IO technology to identify targets that impact immune function, addressing the major challenge of supplying next generation immunomedicines for patients that do not respond to current cancer therapies.

Context Announces Presentation of New Preclinical Data on Apristor in Combination with a Cdk4/6 Inhibitor at San Antonio Breast Cancer Symposium

On November 13, 2018 Context Therapeutics, a clinical-stage biotechnology company, reported that new preclinical data on Apristor, its first-in-class full progesterone receptor antagonist, will be featured at the San Antonio Breast Cancer Symposium taking place on December 4-8, 2018 in San Antonio, TX (Press release, Context Therapeutics, NOV 13, 2018, View Source [SID1234531332]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

At the conference, Dr. Deepak Lala, Ph.D., Chief Technology Officer of Context Therapeutics will present preclinical data highlighting Apristor in inhibiting breast cancer cell proliferation alone or when combined with Palbociclib, a CDK4/6 inhibitor or FASLODEX (Fulvestrant), an estrogen receptor antagonist. The study was conducted in collaboration with Dr. Carol Lange, Ph.D., Tickle Family Chair of Breast Cancer Research at the University of Minnesota,

The poster details are as follows:

Poster Title: The pure progesterone receptor (PR) antagonist onapristone enhances the anti-proliferative effects of CDK4/6 inhibitors in preclinical in-vitro breast cancer models

Poster: #926

Session Date: Saturday, 12/8/201

Session Time: 7:30 AM – 9:00 AM CT

Location: Henry B Gonzalez Convention Center/ Poster Hall 1

For more information on SABCS 2018, please visit View Source

About Apristor

Apristor (onapristone extended release) is Context’s wholly owned, first-in-class, orally active extended release formulation of onapristone, a full progesterone receptor antagonist. Progesterone receptor [PR] plays a critical role in driving breast cancer disease progression as well as therapeutic resistance to first line antiestrogen or Cdk4/6 inhibitor therapy. Apristor is the only full PR antagonist that is being developed to target breast cancer. Apristor has the potential to transform the treatment of breast cancer, through the potent inhibition of PR signaling thereby blocking breast cancer cell proliferation and overcoming resistance to first line antiestrogen and Cdk4/6 inhibitor therapy.

Evotec AG reports first nine-month 2018 results and corporate updates

On November 13, 2018 Evotec AG (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported financial results and corporate updates for the first nine months of 2018 (Press release, Evotec, NOV 13, 2018, View Source;announcements/press-releases/p/evotec-ag-reports-first-nine-month-2018-results-and-corporate-updates-5747 [SID1234531238]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

SIGNIFICANT UPSWING IN FINANCIAL PERFORMANCE
Group revenues: 57% increase to € 270.0 m (9M 2017: € 171.5 m);
EVT Execute revenues up 53% to € 254.3 m (9M 2017: € 165.8 m);
EVT Innovate revenues up 55% to € 51.3 m (9M 2017: € 33.2 m)
Adjusted Group EBITDA up 77% to € 68.7 m (9M 2017: € 38.9 m);
Adjusted EBITDA for EVT Execute of € 62.1 m (9M 2017: € 41.4 m);
Adjusted EBITDA for EVT Innovate of € 6.6 m (9M 2017: € (2.5) m)
Group R&D expenses increase of 67% to € 20.9 m (9M 2017: € 12.5 m) following acquisition of infectious disease unit Evotec ID (Lyon)
Very strong performance in Q3 2018 due to growth in base business, Aptuit contribution, and significant milestone achievements
Strong liquidity position of € 168.6 m even after 50% (€ 70 m) repayment of acquisition loan

EVT EXECUTE – DELIVERING
Clinical Phase I and Phase II starts and good progress within ongoing alliances (e.g. Bayer endometriosis/chronic cough alliance)
Signing of multiple new and extended drug discovery and development agreements (e.g. CHDI, Novo Nordisk, Ferring (after period-end))
New contracts and increased demand for INDiGO solutions and development services (e.g. Ankar, Astex, Inflazome, Yumanity)
Strong performance across all business and service lines (e.g. high-throughput ADME-tox testing at Cyprotex, an Evotec company)

EVT INNOVATE – "JUST THE BEGINNING…"
Two new strategic long-term partnerships with Celgene in oncology (upfront payment: $ 65 m) and targeted protein degradation (financials undisclosed)
Acquisition of Evotec ID (Lyon) creating largest global footprint in infectious disease capabilities with established project pipeline; upfront payment of € 60 m and R&D cost coverage for the first five years
Important milestone achievements in iPSC-based alliances (diabetes alliance with Sanofi, neurodegeneration alliance with Celgene) and further expansion of iPSC platform
Academic BRIDGE model growing (e.g. selection of funded projects under LAB282, LAB150 and LAB591; initiation of French BRIDGE LAB031 with Sanofi)
Participation in additional financing rounds of Forge Therapeutics, FSHD Unlimited, and Topas Therapeutics

CORPORATE
Conversion into European Company (SE) on track
Change in Management Board as of 01 January 2019: Appointment of Dr Craig Johnstone as new COO; Dr Mario Polywka retiring from Evotec
Evotec share listed in MDAX and STOXX Europe 600

GUIDANCE 2018 CONFIRMED
All elements of the financial guidance confirmed

1. SIGNIFICANT UPSWING IN FINANCIAL PERFORMANCE

Evotec’s Group revenues for the first nine months of 2018 grew to € 270.0 m, a significant increase of 57% compared to the same period of the previous year (9M 2017: € 171.5 m, restated). This increase is due to a strong performance in the base business, the positive Aptuit contribution (Jan-Sep 2018: € 83.6 m) as well as increased milestone achievements in existing alliances. The total revenues from milestones, upfronts and licences for the first nine months of 2018 amounted to € 27.2 m and increased by 29% over the same period of the previous year (9M 2017: € 21.1 m). In the first nine months of 2018, the gross margin was 31.0% (9M 2017: 34.8%), reflecting a new business mix with different margin expectations following the acquisition of Aptuit, higher amortisation of intangible assets and adverse FX effects. Gross margin excluding total amortisation of acquisitions amounted to 34.3%.

Q3 2018 delivered a very strong financial performance. Group revenues increased by 43% to € 96.3 m (Q3 2017: € 67.2 m), following growth in the base business, the Aptuit contribution and strong milestone achievements. The significant milestone achievements are reflected in the gross margin of Q3 2018 of 34.7% (Q3 2017: 33.4%). Q3 2018 gross margin excluding total amortisation amounted to 37.7% (Q3 2017: 34.6%). In Q3 2018, an income from bargain purchase of € 15.4 m (Q3 2017: € 0 m) was recorded for the acquisition of Evotec ID (Lyon) as the purchase price was below the net assets required. This one-time effect in 2018 was not allocated to segments and does not impact the adjusted EBITDA. The purchase price allocation is still preliminary. The adjusted Group EBITDA increased from € 12.7 m in Q3 2017 to € 30.1 m in Q3 2018.

Group R&D expenses for the first nine months of 2018 increased as expected by 67% to € 20.9 m (9M 2017: € 12.5 m) mainly following the cost of new strategic efforts in infectious diseases through the acquisition of Evotec ID (Lyon). The additional ID-related R&D expenses are covered by other operating income in context of the new agreement with Sanofi. Furthermore, R&D expenses in the first nine months of 2018 focused on initiatives in the field of iPSC research, R&D platforms as well as academic BRIDGEs. SG&A expenses for the first nine months of 2018 increased as expected by 39% to € 40.8 m (9M 2017: € 29.3 m) mainly due to the additional expenses of Aptuit and Evotec ID (Lyon), an increased headcount in response to the overall Company growth as well as M&A-related expenses. Q3 2018 SG&A expenses remained on a similar level as in prior quarters following the Aptuit acquisition in August 2017.

In the first nine months of 2018, Evotec recorded impairments of intangible assets of € 4.2 m in total (9M 2017: € 1.2 m), following the full impairments of the EVT770 programme (€ 4.0 m) and of the developed assets within the Panion joint venture (€ 0.2 m). At the same time, correlated earn-out accruals of € 2.3 m were relieved under other operating income, which is a counter-effect to the impairment.

Evotec’s adjusted Group EBITDA in the first nine months of 2018 significantly increased by 77% to € 68.7 m (9M 2017: € 38.9 m). Evotec’s operating result for the first nine months of 2018 amounted to € 59.5 m (9M 2017: € 25.5 m). The net result in the first nine months of 2018 increased to € 52.3 m (9M 2017: € 12.7 m).

Liquidity, which includes cash and cash equivalents (€ 135.1 m) and investments (€ 33.5 m) amounted to € 168.6 m at the end of September 2018 (31 December 2017: € 91.2 m) and remained very strong even after the repayment of 50% (€ 70 m) of the Aptuit acquisition loan in the first nine months of 2018. In the first nine months of 2018, Evotec participated in further financing rounds of Forge Therapeutics, FSHD Unlimited, and Topas Therapeutics.

In the first nine months of 2018, revenues from the EVT Execute segment amounted to € 254.3 m, an increase of 53% compared to the same period of the previous year (9M 2017: € 165.8 m). This increase is attributable to the significant upswing in the base business and the Aptuit contribution for the first nine months of 2018. Included in this amount are € 35.6 m of intersegment revenues (9M 2017: € 27.4 m). The EVT Execute segment recorded a gross margin of 24.6% (9M 2017: 28.7%). The drivers behind this change in gross margin are the same drivers affecting the Group gross margin. In the first nine months of 2018, the EVT Execute segment recorded a significant increase of its adjusted EBITDA of 50% to € 62.1 m against the prior-year period (9M 2017: € 41.4 m).

In the first nine months of 2018, the EVT Innovate segment generated third-party revenues of € 51.3 m (9M 2017: € 33.2 m). This 55% increase in EVT Innovate revenues resulted from signing of new partnerships and milestone achievements in key alliances. The EVT Innovate segment reported a gross margin of 48.8% compared to 46.2% in the prior-year period. R&D expenses for EVT Innovate increased from € 15.3 m in the first nine months of 2017 to € 24.1 m in the first nine months of 2018, the increase mainly resulting from the new efforts in infectious diseases in Lyon. The significant growth of revenues and improved margins of the EVT Innovate segment resulted in a positive adjusted EBITDA of € 6.6 m (9M 2017: € (2.5) m).

2. EVT EXECUTE & EVT INNOVATE
EVT EXECUTE
The EVT Execute segment achieved strong progress in existing alliances and signed and started new and expanded established alliances (e.g. CHDI, Novo Nordisk, Ferring (after period-end)). In the multi-target alliance with Bayer, further promising small molecules for the treatment of endometriosis advanced into Phase I and for the treatment of chronic cough into Phase II. Since the beginning of the collaboration in 2012, six first-in-class/best-in-class pre-clinical candidates have been generated, from which three programmes have progressed into Phase I/Phase II clinical trials.

The Aptuit integration into the Evotec Group is on track. In the first nine months of 2018, Evotec was able to sign various new INDiGO agreements with Ankar, Astex, Carna Biosciences, Inflazome, and Yumanity, among others. The INDiGO offering, an integrated and highly efficient process to IND submission, was part of the strategic rationale behind the Aptuit acquisition and was launched by Evotec in March 2018. In addition, Aptuit’s stand-alone development services and integrated CMC continued to deliver and sign new programmes. The high-throughput ADME-tox testing business of Cyprotex (acquired in December 2016) continued its excellent performance of the previous quarters.

EVT INNOVATE
In the first nine months of 2018, the EVT Innovate segment gained significant momentum through signing new deals and achieving critical milestones, resulting in a very strong performance and excellent scientific progress of the segment.

Two new strategic, long-term partnerships were forged with Celgene in the first nine months of 2018. Evotec’s new partnership with Celgene in oncology (initiated in May 2018; upfront payment of $ 65 m) leverages Evotec’s phenotypic screening capabilities and unique compound libraries as well as associated target deconvolution capabilities. Evotec’s third partnership with Celgene is focused on targeted protein degradation (initiated in September 2018; undisclosed upfront payment) which allows the pursuit of high-value drug targets via a novel mechanism of action, which previously have been ‘undruggable’ targets. In this field, Evotec is leveraging in particular its proprietary Panomics and PanHunter platforms.

Furthermore, effective 01 July 2018, Evotec acquired Sanofi’s infectious disease unit in Lyon, triggering an upfront of € 60 m (€ 42 m in cash plus € 18 m cash of the acquired company). This acquisition provides Evotec with the largest global footprint in infectious disease capabilities in the industry and a broad pipeline of drug candidates and discovery projects.

Evotec’s partnered programmes are progressing well as demonstrated by significant milestone achievements in its strategic iPSC alliances with Sanofi in the field of diabetes (TargetBCD) and with Celgene in neurodegeneration. Evotec continues to place great emphasis on the expansion and development of its iPSC platform and patient-centric approaches to drug discovery.

In addition, Evotec’s academic BRIDGE model continues to attract significant interest from academia and industry partners. LAB031, the first French BRIDGE, was formed in October 2018 (after period-end) in partnership with Sanofi. Evotec’s existing BRIDGEs LAB282, LAB150 and LAB591 also recorded progress with projects selected for future activities in the course of the first nine months of 2018.

3. CORPORATE
CONVERSION INTO EUROPEAN COMPANY (SE) ON TRACK
Mandatory negotiation processes with a Special Negotiation Board (SNB) are ongoing regarding the future arrangements for employee involvement, after which Evotec AG will be transferred into Evotec SE with the registered seat and headquarters remaining in Hamburg, Germany.

CHANGE IN MANAGEMENT BOARD AS OF 01 JANUARY 2019: APPOINTMENT OF DR CRAIG JOHNSTONE AS NEW COO; DR MARIO POLYWKA RETIRING
Following the departure of Dr Mario Polywka as Evotec’s COO effective 31 December 2018, the Supervisory Board of Evotec will appoint Dr Craig Johnstone as its new Chief Operating Officer and member of the Management Board, effective 01 January 2019. Dr Johnstone is a successful drug discovery leader with over 20 years’ experience. Dr Johnstone joined Evotec in May 2012 as SVP Drug Discovery and Innovation Efficiency and was appointed Directeur General and Site Head, Evotec France, in April 2015. In January 2017, he was appointed Global Head, Integrated Drug Discovery at Evotec. Between 1994 and 2012, Dr Johnstone served in a number of projects, functions, matrix and leadership roles at AstraZeneca, Prosidion and Rapier Research. He holds a BSc in Chemistry and a PhD in organic and organometallic synthesis and has published more than 70 patents.

Dr Werner Lanthaler, Chief Executive Officer of Evotec, commented: "On behalf of the Management Board and the Company, I would like to sincerely thank Mario for his outstanding contributions, strong commitment to the Company and very valuable insights, which helped Evotec to become the leader in external innovation. He has been an essential part of our Management Team and we are very thankful for him being such a passionate force driving Evotec’s development. We will closely stay in touch with him and we wish him all the best for all of his future endeavours, amongst others remaining a consultant to Evotec. Moreover, I am delighted to welcome Craig to our team as new Chief Operating Officer."

Study Demonstrating Accuracy of DecisionDx-Melanoma Prognostic Test Across Melanoma Tissue Sources Presented at the American Society of Dermatopathology 55th Annual Meeting

On November 13, 2018 Castle Biosciences, Inc., the skin cancer diagnostics company providing molecular diagnostics to improve cancer management decisions, reported study results showing that the DecisionDx-Melanoma test accurately predicts risk for patients with cutaneous melanoma when using either biopsy or wide local excision (WLE) as the tissue source (Press release, Castle Biosciences, NOV 13, 2018, View Source [SID1234531257]). Highlights of the study were presented during an oral presentation at the American Society of Dermatopathology 55th Annual Meeting held November 8-11, 2018 in Chicago.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This study demonstrates that the DecisionDx-Melanoma test provides an accurate, independent prediction of risk regardless of tissue source," said Sarah Estrada, M.D., FACP, Affiliated Dermatology, Scottsdale AZ, a study investigator. "Using biopsy or wide local excision tissue does not impact the ability of the DecisionDx-Melanoma test to accurately predict risk and inform patient management decisions."

Study Background

The DecisionDx-Melanoma test has been shown to provide an accurate, independent prediction of risk for patients with cutaneous melanoma.
The test has shown robust analytic reliability with 99% inter-assay concordance and 100% intra-assay concordance. Technical success exceeded 98% on samples with sufficient tumor content.
This study assessed whether test results or patient outcomes were associated with tissue source (biopsy or WLE) in an archival cohort of 537 patients with Stage I-III cutaneous melanoma for whom the tissue source was known.
Key Study Results

Among those who had biopsy tissue tested, a higher percentage had Stage I disease (68%) compared to those who had WLE tissue tested (19% Stage I; p<0.001).
Patients who had WLE tissue tested were significantly more likely to have Stage III melanoma (50%) compared to those who had biopsy tissue tested (17% Stage III; p<0.001).
Patients who had WLE tissue tested also were more likely to have higher risk pathologic features such as ulceration and increased Breslow thickness.
For both tissue sources, patients who had the lowest risk DecisionDx-Melanoma test result (Class 1A) had significantly improved distant metastasis-free survival and melanoma-specific survival rates compared to those who had the highest risk test result (Class 2B).
After adjusting for pathologic features among patients in the two tissue source groups, use of WLE tissue was not significantly associated with DecisionDx-Melanoma test class result.
In multivariate analysis, DecisionDx-Melanoma Class 2B (highest risk) was a significant independent predictor of recurrence, distant metastasis and melanoma-specific survival, while WLE tissue source was not found to be predictive of outcomes.
These results demonstrate that the DecisionDx-Melanoma test provides an accurate, independent prediction of risk regardless of tissue source.
About DecisionDx-Melanoma

The DecisionDx-Melanoma test uses tumor biology to predict individual risk of melanoma recurrence and sentinel lymph node positivity independent of traditional factors. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multi-center studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in four prospective studies including 702 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,300 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included over 1,400 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in multi-center and single-center studies. More information about the test and disease can be found at www.SkinMelanoma.com.

Syros Presents New Preclinical Combination Data on SY-1365 and First Preclinical Data from Oral CDK7 Inhibitor Program at EORTC-NCI-AACR Meeting

On November 13, 2018 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported preclinical data on SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, showing synergistic anti-tumor activity in combination with carboplatin, a standard-of-care therapy, in models of ovarian cancer and providing a mechanistic rationale for the ongoing investigation of the combination in the Phase 1 clinical trial of SY-1365 (Press release, Syros Pharmaceuticals, NOV 13, 2018, View Source [SID1234531258]). The Company also announced the first preclinical data on its class of highly selective oral CDK7 inhibitors, which showed significant anti-proliferative activity in preclinical models of breast and ovarian cancers. These data were presented at the 30th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium in Dublin.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Selective CDK7 inhibition represents a potentially transformative approach for treating a range of cancers that have eluded effective treatment," said Eric R. Olson, Ph.D., Syros’ Chief Scientific Officer. "Our presentations at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) meeting highlight our leadership in the field and support the ongoing clinical development of SY-1365 as well as the selection of SY-5609, a highly selective oral CDK7 inhibitor, as our next development candidate. Given the broad potential of CDK7 inhibitors as a new class of medicines, we believe physicians and patients will seek options across multiple modalities and believe an oral molecule could serve as an important complement to SY-1365. We are committed to maximizing the potential of CDK7 inhibition for patients, as we work to achieve our vision of developing new medicines that provide profound benefit for patients."

SY-1365 Preclinical Combination Data
The preclinical data presented at EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) provide a strong mechanistic rationale for the ongoing clinical investigation of SY-1365 in combination with carboplatin in ovarian cancer patients. Homologous recombination deficiency (HRD), a cellular defect caused by the disruption of normal DNA damage repair processes, sensitizes cells to treatment with DNA repair inhibitors, including PARP inhibitors and DNA-damaging agents such as carboplatin. In preclinical models of ovarian cancer, SY-1365 was shown to inhibit DNA repair and decrease the expression of homologous recombination repair (HRR) genes, which are important for repairing harmful breaks in DNA. These data suggest that SY-1365 induces an HRD-like state, which may result in enhanced sensitivity to DNA-damaging agents and DNA repair inhibitors.

Consistent with the proposed mechanism-of-action, SY-1365 demonstrated synergy with carboplatin in ovarian cancer cell lines and demonstrated greater anti-tumor activity in combination with carboplatin in xenograft models of ovarian cancer than either agent alone.

Syros is currently conducting a Phase 1 clinical trial assessing the safety and efficacy of SY-1365 as a single agent and in combination with standard-of-care therapies in multiple ovarian and breast cancer patient populations. The ongoing trial includes a study cohort evaluating SY-1365 in combination with carboplatin in ovarian cancer patients who have relapsed after one or more prior therapies. Additional details about the trial can be found using the identifier NCT03134638 at www.clinicaltrials.gov.

Preclinical Data from Oral CDK7 Inhibitor Program
Syros created a suite of highly selective and potent orally available CDK7 inhibitors. The preclinical data at EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) detail for the first time the selectivity, potency and anti-tumor activity of these inhibitors. Using a representative member of Syros’ suite of oral CDK7 inhibitors, these data show:

200- to 1,200-fold greater selectivity for CDK7 over other members of the CDK family, including CDK2, CDK9 and CDK12.
Robust anti-proliferative activity in triple negative breast cancer and ovarian cancer cell lines, which was associated with the induction of apoptosis and cell cycle arrest.
Strong correlation between biochemical potency, CDK7 target engagement and tumor growth inhibition.
Substantial anti-tumor effects in multiple cell-line and patient-derived xenograft models of triple negative breast and ovarian cancers.
These data helped support the selection of SY-5609 as the Company’s next development candidate. Syros is currently advancing SY-5609 into Investigational New Drug (IND) application-enabling preclinical studies.

The poster presentations on the SY-1365 preclinical combination data and on the oral CDK7 inhibitor program are now available on the Publications and Abstracts section of the Syros website at www.syros.com.