On April 1, 2019 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported its results from the Phase 1b portion of the ProSTAR clinical trial of CPI-1205 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in Atlanta (Press release, Constellation Pharmaceuticals, APR 1, 2019, View Source [SID1234534873]). Poster CT094/18, ProSTAR: A phase 1b/2 study of CPI-1205, a small molecule inhibitor of EZH2, combined with enzalutamide (E) or abiraterone/prednisone (A/P) in patients with metastatic castration-resistant prostate cancer (mCRPC), was presented at the poster session starting at 1:00 PM EDT today. The Company will present two other posters highlighting its preclinical pipeline later in the AACR (Free AACR Whitepaper) meeting.

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"We are pleased to report the ProSTAR Phase 1b results," said Adrian Senderowicz, Chief Medical Officer. "These results show clinical activity in subsets of a heterogeneous population of advanced mCRPC patients in combination with either abiraterone or enzalutamide. Activity was particularly noteworthy in patients taking CPI-1205 in combination with abiraterone, an agent where responses in second-line patients have historically been poor, and in AR-V7-negative patients. Based on the entirety of the results, we initiated the Phase 2 portion of the trial in late 2018 to better define the patient populations most likely to benefit from CPI-1205. We look forward to reporting initial Phase 2 data in the second half of 2019."

The poster presentation included the following highlights from the Phase 1b portion of ProSTAR, using a February 6, 2019, data cutoff:

Baseline Characteristics

The Phase 1b portion of ProSTAR enrolled 36 patients: 20 in the CPI-1205 + abiraterone arm and 16 in the CPI-1205 + enzalutamide arm.

Each arm studied two different dose regimens of CPI-1205 as part of the combination: 800 mg three times daily or 400 mg twice daily + cobicistat (to block CYP3A4).

The Phase 1b portion of ProSTAR was conducted in a heterogeneous patient population who had been treated with a variety of treatment regimens, including chemotherapy. As such, a significant proportion of patients had indicators of poor prognosis at baseline. Of the 36 patients enrolled, 13 (36%) were positive for Androgen Receptor Splice Variant 7, or AR-V7, isoforms (proteins with similar structures); 20 (56%) had unfavorable circulating tumor cell counts; 13 (36%) had previously received chemotherapy; and 18 (50%) had abnormal levels of lactate dehydrogenase (an enzyme in the blood that can indicate tissue damage, cancer, or some noncancerous conditions) at baseline.

Because patients without AR-V7 isoforms have tended to respond better to ARS inhibition than those with AR-V7 isoforms, and given the hypothesis that ARS inhibition acts synergistically with EZH2 inhibition, patients without AR-V7 isoforms may be more likely to benefit from the potential synergistic effect of CPI-1205 with ARS inhibitor therapy.

Clinical Activity

Clinical activity was observed in both the enzalutamide and abiraterone arms, including ³50% PSA reductions and an objective response by RECIST 1.1 criteria.

All PSA responses seen in the trial were ³80%, deeper than the ³50% reduction endpoint in the trial. All PSA responses were found in AR-V7-negative patients. Two out of 18 patients in the abiraterone arm achieved PSA reductions of more than 80%. Patients being treated with abiraterone after enzalutamide historically have been shown to achieve poor PSA responses and rapid time to disease progression. PSA responses are summarized below:

³80% PSA
Reductions in
AR-V7-Positive
Patients ³80% PSA
Reductions in
AR-V7-Negative
Patients
CPI-1205 + abiraterone**

0/8* (0%) 2/10* (20%)
CPI-1205 + enzalutamide**

0/5 (0%) 3/11 (27%)

*
2 patients not evaluable for PSA response

Includes patients treated with CPI-1205 800 mg three times daily and CPI-1205 400mg twice daily + cobicistat

The majority of patients with measurable lesions achieved durable disease control during the study, as follows:

Partial
Response Stable
Disease Disease
Control Rate of
Any Duration Disease
Control Rate
³3 Months
CPI-1205 + abiraterone

0/8 (0%) 6/8 (75%) 6/8 (75%) 4/8 (50%)
CPI-1205 + enzalutamide

1/5 (20%) 2/5 (40%) 3/5 (60%) 3/5 (60%)
Several patients achieved disease control that exceeded or was approaching six months at the data cutoff while continuing therapy.

Safety

CPI-1205 was generally well tolerated in combination with enzalutamide or abiraterone. The most common treatment-related adverse events (³20%) were fatigue, diarrhea, and nausea, which were usually mild to moderate in severity and manageable with supportive care. In combination with enzalutamide, treatment-related adverse events ³ Grade 3 included fatigue, nausea, and increased ALT (n=1; 6.3%, respectively). In combination with abiraterone, treatment-related adverse events ³ Grade 3 included fatigue and increased ALT (n=1; 5%, respectively). For more details, please see the poster here.

Pharmacokinetics/Pharmacodynamics (PK/PD)

Patients in two treatment arms were dosed with 800 mg of CPI-1205 three times daily with enzalutamide or abiraterone. Patients in the other two arms were dosed with 400 mg of CPI-1205 twice daily in combination with cobicistat, a CYP3A4 inhibitor, and enzalutamide or abiraterone. While the Company observed in the trial that cobicistat increased the exposure of CPI-1205, the Company did not observe meaningful differences in pharmacodynamics or efficacy compared to 800 mg of CPI-1205 three times daily without cobicistat. Therefore the recommended Phase 2 dose of CPI-1205 for ProSTAR Phase 2 was determined to be 800 mg three times daily.

Phase 2

The Phase 1b portion of ProSTAR was designed primarily to study the safety, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and a recommended Phase 2 dose of CPI-1205 with abiraterone and enzalutamide. Based on the Phase 1b data, the Company initiated the Phase 2 portion of ProSTAR in late 2018. The Phase 2 portion of the trial is evaluating CPI-1205 in combination with an ARS inhibitor as a second-line treatment for patients with mCRPC. The Company will collect and analyze biomarker and other translational data in Phase 2 to better define which patients may be most likely to respond to treatment with CPI-1205. Two randomized arms of Phase 2 are studying CPI-1205 in combination with enzalutamide versus enzalutamide alone.

In addition, because of the activity seen in the abiraterone arm in the Phase 1b portion of ProSTAR, the Company has also initiated a Phase 2 arm to evaluate CPI-1205 in combination with abiraterone in second-line mCRPC patients. According to a recent study by the laboratory of Dr. Kim Chi of the Vancouver Prostate Centre, few patients responded to treatment with abiraterone after experiencing disease progression on enzalutamide. For this reason, we have not instituted an additional control arm. In the Chi study, out of 101 patients receiving abiraterone after experiencing disease progression on enzalutamide, no patients achieved an 80% reduction in PSA levels and only 4% achieved a 50% PSA reduction.1 The patient population in the Chi study had baseline characteristics that are different from those in the Phase 1b portion of ProSTAR, and more similar to those that are expected to be in ProSTAR Phase 2. For example, unlike ProSTAR Phase 1b, in which patients had been previously treated with a range of therapies – including 36% who had received chemotherapy – ProSTAR Phase 2, like the Chi study, is enrolling only patients receiving second-line therapy with no prior chemotherapy in order to focus on activity in that patient population.

The Company expects to provide an initial update from the Phase 2 portion of ProSTAR in the second half of 2019.

For more information on the Phase 1b portion of ProSTAR, please see the poster here.

1
D Khalaf et al., Phase 2 randomized cross-over trial of abiraterone + prednisone (ABI) vs enzalutamide (ENZ) for patients (pts) with metastatic castration resistant prostate cancer (mCRPC): results for 2nd-line therapy, poster presented at 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting.

Discovery Pipeline

Constellation is presenting two additional posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting that speak to the depth and breadth of the Company’s product pipeline and its expertise in epigenetics. Poster 4351/11, Single-cell RNA sequencing reveals transcriptomic heterogeneity in response to epigenetic inhibitors, will be presented at the 1PM-5PM EDT poster session on April 2. Poster 4722/12, Efficacy of novel EP300/CBP histone acetyltransferase inhibitor in hormone responsive breast cancer, will be presented at the 8AM-12PM EDT poster session on April 3.

About ProSTAR

ProSTAR is an open-label Phase 1b/2 clinical trial of CPI-1205, a potent and highly selective small-molecule EZH2 inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) in the second-line setting. The ProSTAR study is evaluating CPI-1205 in combination with either enzalutamide or abiraterone / prednisone ("abiraterone"), which are androgen receptor signaling (ARS) inhibitors, in mCRPC patients who experienced disease progression while receiving the other ARS inhibitor.

About mCRPC

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced form of prostate cancer and is defined by disease progression despite treatment with androgen depletion therapy (ADT). mCRPC may present as one or any combination of the following: a continuous rise in serum levels of PSA, progression of known metastases, or appearance of new metastases. Prognosis is associated with several factors, including the ability to perform certain daily activities and the presence of bone pain. Additional symptoms commonly include anemia (low levels of healthy red blood cells), weight loss,

fatigue, hypercoagulability (abnormal blood coagulation), and increased susceptibility to infection. mCRPC presents as a spectrum of disease, ranging from patients without symptoms but rising PSA levels despite ADT to patients with metastases and significant debilitation.

On April 1, 2019 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported promising preclinical data at the annual AACR (Free AACR Whitepaper) meeting from its next generation SPEAR T-cell targeting MAGE-A4 (Press release, Adaptimmune, APR 1, 2019, View Source;p=RssLanding&cat=news&id=2392937 [SID1234534869]). This next generation SPEAR T-cell, known as ADP-A2M4CD8, expresses the CD8α co-receptor alongside the engineered TCR that targets MAGE-A4.

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Co-expression of CD8α is anticipated to broaden the immune response against solid tumors and increase antitumor activity by converting CD4+ helper cells into CD8+ killer or cytotoxic T-cells. The preclinical data demonstrate that the addition of CD8a with the engineered TCR in vitro improved engagement and function in CD4+ T-cells that may support clonal expansion of CD8+ T-cells, differentiation into effector and memory T-cells, as well as engage the wider immune system in antitumor responses.

"Our next generation programs are designed to enhance our existing SPEAR T-cells, to improve their ability to target and kill solid tumors. The preclinical data we presented at AACR (Free AACR Whitepaper) indicate that adding CD8a to our ADP-A2M4 candidate may help broaden the antitumor immune response against additional tumor antigens. Further, the CD8a co-receptor may enhance the ability of CD4+ SPEAR T-cells to kill cancer cells through the engineered TCR targeting MAGE-A4," said Rafael Amado, Adaptimmune’s President of Research & Development.

Poster presentation details:

Title: Enhanced activity of second-generation MAGE-A4 SPEAR T-cells through co-expression of a CD8α homodimer
Session Title: Adoptive Cell Therapy 2
Session Date and Time: Monday Apr 1, 2019 1:00 PM – 5:00 PM ET
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 22
Poster Board Number: 12
Abstract Number: 2313

On April 1, 2019 OncoCyte Corporation (NYSE American: OCX), a developer of novel, non-invasive tests for the early detection of lung cancer, reported financial and operating results for the fourth quarter and year ended December 31, 2018 and provided a corporate update (Press release, Oncocyte, APR 1, 2019, View Source [SID1234534867]).

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"OncoCyte has made outstanding progress since our last quarterly update to investors, reporting positive results from our DetermaVu R&D Validation Study which demonstrated that DetermaVu is a commercially viable assay with the potential to change the treatment paradigm in lung cancer diagnostics," said William Annett, President and Chief Executive Officer of OncoCyte. "Importantly, these results also confirmed the Company’s unique Immune System Interrogation approach provides an exquisitely sensitive and consistent signal for the diagnosis of early stage lung cancer. We are excited to investigate the broader application of this technology across multiple solid tumors moving forward and remain highly focused on executing the few remaining steps required for commercialization of DetermaVu later this year."

Highlights

Successfully transitioned to the Ion Torrent next-generation sequencing platform for robust and reproducible results

Reported positive results from blinded, prospective R&D Validation Study demonstrating best-in-class performance with sensitivity of 90% and specificity of 75%

R&D Validation study served as proof of concept for unique Immune System Interrogation approach with potential applicability across many types of solid tumors

On-track to complete remaining validation studies by mid-year and make DetermaVu commercially available second half of 2019

Completed a successful equity raise for gross proceeds of $40.25 million which provides the resources to execute the development and commercialization of DetermaVu
Remaining Validation Pathway for DetermaVu:

1H 2019: Analytical Validation – with results expected shortly, this study will establish the performance characteristics of the system as established in the Clinical and Laboratory Standard Institute Guidelines that cover quantitation, precision, reproducibility and interfering substances

1H 2019: CLIA Laboratory Validation study – will rerun between 100 and 120 patient samples previously run in the R&D Validation study to confirm that the same positive results are obtained on the analytically validated systems

Mid-year 2019: Clinical Validation study – will run approximately 300 to 350 blinded, prospectively-collected blood samples to establish the DetermaVu performance in an independent, blinded data set as a final confirmation of test sensitivity and specificity in OncoCyte’s CLIA lab setting

2H 2019: Commercial availability of DetermaVu

Post-launch (2020 initiation): Clinical Utility study – follow-on real world evidence study to demonstrate a net improvement in patient outcomes and cost savings for the healthcare system
Fourth Quarter and Annual 2018 Financial Results

At December 31, 2018, OncoCyte had cash and cash equivalents of $8.0 million and marketable equity securities valued at $0.4 million, for a total of $8.4 million of liquid assets. The balance sheet was strengthened in February 2019 with the successful equity raise of $37.4 million in net proceeds from an underwritten public offering.

For the quarter ended December 31, 2018, OncoCyte reported a net loss of $4.5 million, or ($0.11) per share, compared to a net loss of $4.0 million, or ($0.13) per share, in the fourth quarter of 2017.

For 2018, OncoCyte reported a net loss of $15.8 million, or ($0.42) per share, compared to $19.4 million, or ($0.64) per share, in 2017.

Operating expenses for the three months ended December 31, 2018 were $4.0 million as reported, and were $3.5 million on an as adjusted basis. Operating expenses for 2018 were $15.2 million as reported and were $12.5 million on an as adjusted basis.

The reconciliation between GAAP and non-GAAP operating expenses is provided in the financial tables included with this earnings release.

Research and development expenses for the fourth quarter of 2018 were $1.2 million compared to $1.5 million for the same period in 2017, a decrease of $0.3 million. Research and development expenses for the year ended December 31, 2018 were $6.5 million, compared to $7.2 million during 2017, a decrease of $0.7 million. The decreases were primarily attributable to laboratory and other expenses related to diagnostic tests for diseases other than lung cancer as OncoCyte devoted substantially all of its research and development efforts to DetermaVu during 2018.

General and administrative expenses for the fourth quarter of 2018 were $2.6 million compared to $1.8 million for the same period in 2017. The $0.8 million increase was mainly attributable to personnel and related compensation, primarily related to the hiring of OncoCyte’s Chief Financial Officer and its Chief Operating Officer.

General and administrative expenses for the year ended December 31, 2018 decreased to $7.0 million from $9.2 million during 2017, a decrease of $2.2 million. During the year ended December 31, 2017, OncoCyte incurred a noncash expense of $4.1 million for the issuance of new warrants to certain investors who exercised outstanding warrants. OncoCyte did not incur a similar expense during 2018. Personnel and related compensation expenses increased by $1.1 million during 2018, primarily related to the hiring of the executives noted above, an increase of $0.5 million in legal, investor relations, financing and other related expenses, and an increase of $0.3 million in noncash stock-based compensation expense due to increased stock option grants.

Sales and marketing expenses for the fourth quarter of 2018 were $0.3 million compared to $0.6 million for the same period in 2017, a decrease of $0.3 million. Sales and marketing expenses for the full-year 2018 were $1.7 million compared to $2.4 million during 2017, a decrease of $0.7 million. These decreases were primarily due the decrease in consulting, marketing, and related expenses as OncoCyte concentrated its resources on the development of DetermaVu rather than on marketing related activities.

Conference Call

The Company will host a conference call today, April 1, 2019, at 4:30 pm EDT / 1:30 pm PDT to discuss the results along with recent corporate developments.

The dial-in number in the U.S./Canada is 877-407-9716; for international participants, the number is 201-493-6779. For all callers, please refer to Conference ID 13689139. To access the live webcast, go to the investor relations section on the Company’s website, View Source

About DetermaVu

DetermaVu is being developed as an intermediate step to confirm the absence of cancer after imaging modalities (LDCTs) that detect suspicious lung nodules and before downstream invasive procedures that determine if the nodules are malignant. OncoCyte estimates that a $4.7 billion annual market could develop in the U.S. for its confirmatory lung cancer liquid biopsy test, depending on market penetration and reimbursable pricing.

DetermaVu has the potential to dramatically reduce U.S. healthcare costs by billions of dollars each year by eliminating unnecessary biopsies, which, according to a recent Medicare study, cost on average $14,634 each. In addition, DetermaVu can provide great benefit to patients by avoiding invasive biopsies and the complications that arise in up to 24% of those procedures, and deaths that occur in up to 1% of cases.

DetermaVu is a trademark of OncoCyte Corporation.

On April 1, 2019 Xenetic Biosciences, Inc. (NASDAQ: XBIO) ("Xenetic" or the "Company"), a clinical-stage biopharmaceutical company focused on the discovery, research and development of next-generation biologic drugs and novel orphan oncology therapeutics, reported its financial results for the year ended December 31, 2018 (Press release, Xenetic Biosciences, APR 1, 2019, View Source [SID1234534866]).

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Xenetic also provided a corporate update and reviewed plans related to the Company’s recently announced agreement to acquire a novel CAR T ("Chimeric Antigen Receptor T Cell") platform technology, called "XCART", as well as its oncology therapeutic XBIO-101 (sodium cridanimod), a small-molecule immunomodulator and interferon inducer which, in preliminary studies has been shown to increase progesterone receptor ("PrR") expression in endometrial tumor tissue.

"Upon closing of our recent transformative agreement to acquire XCART, our differentiated CAR T platform technology, Xenetic will be positioned at the forefront of innovation in the development of new oncology therapeutics where there remains significant unmet need," commented Jeffrey Eisenberg, Chief Executive Officer of Xenetic. "Over the course of 2019, we plan to focus our R&D efforts initially on leveraging the XCART platform to develop cell-based therapeutics for the treatment of B-cell Non-Hodgkin lymphomas, an initial global market opportunity estimated to exceed $5 billion per year.1 I believe we are well positioned to build momentum and evolve Xenetic into a significant player in the oncology space, which will ultimately drive meaningful value for shareholders."

XCART Technology

On March 1, 2019, the Company entered into agreements to acquire the novel XCART platform technology, a proximity-based screening platform capable of identifying CAR constructs that can target patient-specific tumor neoantigens, with a demonstrated proof of mechanism in B-cell Non-Hodgkin lymphomas. The XCART technology, developed by The Scripps Research Institute in collaboration with the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, is believed to have the potential to significantly enhance the safety and efficacy of cell therapy for B-cell lymphomas by generating patient- and tumor-specific CAR T cells. The acquisition is subject to conditions typical for a transaction of this kind, including appropriate stockholder approvals, and is expected to close in the first half of 2019.

The XCART technology platform was designed by its originators to utilize an established screening technique to identify peptide ligands that bind specifically to the unique B-cell receptor ("BCR") on the surface of an individual patient’s malignant tumor cells. The peptide is then inserted into the antigen-binding domain of a CAR, and a subsequent transduction/transfection process is used to engineer the patient’s T cells into a CAR T format which redirects the patient’s T cells to attack the tumor. Essentially, the XCART screening platform is the inverse of a typical CAR T screening protocol wherein libraries of highly specific antibody domains are screened against a given target. In the case of XCART screening, the target is itself an antibody domain, and hence highly specific by its nature. The XCART technology creates the possibility of personalized treatment of lymphomas utilizing a CAR with an antigen-binding domain that should only recognize, and only be recognized by, the unique BCR of a particular patient’s B-cell lymphoma.

An expected result for XCART is limited off-tumor toxicities, such as B-cell aplasia. Xenetic’s clinical development program will seek to confirm the early preclinical results, and to demonstrate a more attractive safety profile than existing therapies.

Once the acquisition is consummated, the Company intends to pursue development efforts of the XCART technology as well as other development efforts in the area of CAR T therapy.

XBIO-101 Program Update

XBIO-101 is the Company’s most advanced investigational drug candidate with an Orphan Drug designation from the FDA for the potential treatment of progesterone receptor negative endometrial cancer in conjunction with progesterone therapy. The Company’s Phase 2 clinical trial for XBIO-101 commenced patient dosing in October 2017. The trial targets a population of patients who have either failed progestin monotherapy or who have been identified as having progesterone receptor negative ("PrR-") tumors. The Company closed patient enrollment of the trial in March 2019 as a result of slower than expected progress on the trial resulting from patient enrollment and retention challenges.

Xenetic is currently in the process of identifying development paths for XBIO-101, particularly those that can efficiently leverage the existing human data and regulatory status to extend development into immuno-oncology settings.

Summary of Financial Results for Fiscal Year 2018

Net loss for the year ended December 31, 2018, was approximately $7.3 million. The Company had an accumulated deficit of $153.2 million at December 31, 2018 as compared to an accumulated deficit of approximately $145.9 million at December 31, 2017. Working capital (deficit) was approximately $(0.4) million and $3.9 million at December 31, 2018 and December 31, 2017, respectively. During the year ended December 31, 2018, the Company’s working capital decreased by $4.3 million due primarily to outflows for general operating costs and costs related to our XBIO-101 Phase 2 clinical trial. These cash outflows were partially offset by approximately $1.5 million of proceeds received from the exercise of warrants during the year ended December 31, 2018.

The Company ended the year with approximately $­0.6 million of cash. Subsequent to year-end, on March 7, 2019, the Company completed a registered direct offering of common stock with gross proceeds of approximately $3.1 million before deducting placement agent fees and other offering expenses.

On April 1, 2019 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage immunotherapy company developing the next generation of novel T cell therapies for patients suffering from cancer, reported financial results for the fourth quarter and full year ended December 31, 2018 and provided a corporate update (Press release, TCR2 Therapeutics, APR 1, 2019, View Source [SID1234534865]).

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"TCR2 has achieved important scientific, clinical, and operational milestones over the past year," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "Although adoptive T cell therapies have made significant progress in the fight against cancer, our TRuC platform has the potential to both improve upon existing options and expand their use. TC-210 has cleared its IND and we have initiated our Phase 1/2 clinical trial, with initial data expected later this year. We also remain on track to submit an IND for TC-110 in the second half of 2019. In February, we successfully completed our initial public offering, a significant step for the Company which further strengthened our financial position."

2018 Corporate Highlights

Advanced TC-210, TCR2’s lead T cell receptor (TCR) Fusion Construct T cell (TRuC T cell) product candidate, to investigational new drug (IND) application submission in December 2018 and IND clearance by the U.S. Food and Drug Administration (FDA) in January 2019. TCR2 engineered TC-210 T cells to target and kill mesothelin-expressing cancers while engaging the entire TCR, independent of human leukocyte antigens (HLA). In preclinical studies, TC-210 has demonstrated better anti-tumor activity, longer persistence, and lower cytokine release compared to chimeric antigen receptor (CAR)-T cells engineered with the same mesothelin binder. TCR2 initiated a Phase 1/2 clinical trial for TC-210 to treat patients with mesothelin-positive solid tumors, including non-small cell lung cancer (NSCLC), ovarian cancer, malignant pleural/peritoneal mesothelioma, and cholangiocarcinoma. TCR2 expects to generate its first clinical data for TC-210 in the second half of 2019.

Expanded the TCR2 pipeline, initiating IND-enabling studies for TC-110 and TC-220 product candidates, and building next-generation enhancements into the TRuC platform.

TC-110 is a CD19 targeted TRuC-T cell product candidate designed to treat patients with CD19-positive B-cell hematological malignancies, including diffuse large B-cell lymphoma (DLBCL), adult acute lymphoblastic leukemia (aALL), follicular lymphoma (FL), and other non-Hodgkin lymphoma (NHL) subtypes. In preclinical studies, TC-110 has shown better anti-tumor activity and persistence compared to CD28 and 4-1BB CAR-T cells engineered with the same CD19 binder, while also exhibiting lower levels of cytokine release.

TC-220 is a MUC16 (Mucin 16, Cell Surface Associated)-targeted TRuC-T cell product candidate designed to treat patients with MUC16-positive solid tumors. MUC16 is highly expressed in many solid tumors, including ovarian, pancreatic, gastric, and colorectal cancers. TC-220 has shown strong anti-tumor activity in preclinical models of MUC16-positive ovarian cancers. TCR2 plans to file an IND for TC-220 in the first half of 2020.

TCR2 is developing several additional tools that may be incorporated into future TRuC product candidates to overcome tumor defense mechanisms, including dual-antigen targeting and strategies to counter the immunosuppressive microenvironment of solid tumors. TCR2 is also evaluating multiple proprietary designs for allogeneic, or off the shelf, TRuC-T cells.

Established semi-automated Good Manufacturing Practice (GMP) manufacturing process. TCR2 currently manufactures GMP-grade clinical lots for TC-210 through third-party contractors. In December 2018, TCR2 entered into an agreement with Cell and Gene Therapy (CGT) Catapult Limited (Catapult), which will allow TCR2 to manufacture TRuC-T cells using its own personnel at CGT Catapult’s facility in Stevenage, UK. The TCR2 CGT Catapult facility is expected to be operational in the second half of 2019. At full capacity, TCR2 estimates this facility would expand its manufacturing capacity to a total of approximately 400 treatments per year.

Raised $125 million in an oversubscribed Series B financing round in March 2018. The financing was co-led by 6 Dimensions Capital and Curative Ventures with participation from new investors Redmile and Arrowmark and all of TCR2’s Series A investors.

Strengthened its management and board in 2018. This included adding Ian Somaiya as Chief Financial Officer, along with Neil Gibson Ph.D. and Andrew Allen M.D., Ph.D. to the Board of Directors.

Recent Developments

In January 2019, the FDA cleared the IND for TC-210. TCR2 initiated its Phase 1/2 trial to treat patients with NSCLC, ovarian cancer, malignant pleural/peritoneal mesothelioma, and cholangiocarcinoma. TCR2 expects to generate initial data from the trial in the second half of 2019.

In February 2019, TCR2 completed an initial public offering pursuant to which it issued and sold 5,750,000 shares of common stock, including full exercise of the underwriters’ over-allotment option, resulting in net proceeds of $80.2 million after deducting underwriting discounts and commissions and other offering expenses.

In February 2019, the FDA granted orphan drug designation to TC-210 for the treatment of mesothelioma.

TCR2 recently held a pre-IND meeting with the FDA and remains on track to submit an IND for TC-110 in the second half of 2019.

In February 2019, the United States Patent and Trademark Office issued U.S. Patent No.: 10,208,285, with claims covering TCR2’s TRuC-T cells that express anti-mesothelin TCR fusion proteins, including TC-210.

Anticipated Milestones
TCR2 plans to advance its first three TRuC-T cell product candidates into clinical trials by the first half of 2020, while also establishing and expanding its manufacturing capabilities through its collaboration with CGT Catapult.

TC-210 – release initial Phase 1 data from the Phase 1/2 trial in 2H 2019.

TC-110 – IND submission in 2H 2019.

TC-220 – IND submission in 1H 2020.

Catapult manufacturing facility – operational in 2H 2019.

Financial Highlights

TCR2 ended 2018 with $123.2 million in cash, cash equivalents, and investments compared to $19.8 million as of December 31, 2017. Net cash from financing activities for the year ended December 31, 2018 was $123.0 million compared to $16.2 for the year ended December 31, 2017. Net cash used in operations was $18.8 million for the year ended December 31, 2018 compared to $12.0 million for the year ended December 31, 2017.

Net loss for the year ended December 31, 2018 was $24.3 million compared to $13.1 million for the year ended December 31, 2017.

Research and development expenses were $19.7 million for the year ended December 31, 2018 compared to $9.6 million for the year ended December 31, 2017. The increase in R&D expenses is primarily related to increase in headcount and preclinical development of our lead solid tumor product candidate, TC-210.
General and administrative expenses were $6.8 million for the year ended December 31, 2018, compared to $3.6 million for the year ended December 31, 2017. The increase in general and administrative expenses was primarily due to an increase in personnel costs.

Upcoming Events
Members of the TCR2 Therapeutics management team are scheduled to present at the following upcoming conferences.

Jefferies Immuno-Oncology Cell Therapy Summit: Alfonso Quintás Cardama, M.D., Chief Medical Officer, will present on Friday, April 5, 2019 at 7:30am in Boston, MA.

4th Annual CAR-T Congress USA: Robert Hofmeister Ph.D., Chief Scientific Officer, will present on Wednesday, April 17, 2019 at 9:40am in Boston, MA.

Class of 2018 Biotech IPOs Investor Day: Ian Somaiya, Chief Financial Officer, will present on Friday, April 26, 2019 at the offices of Davis Polk in New York, NY.

BioTrinity 2019: Garry Menzel, Ph.D., President and CEO, will present on Tuesday, April 30, 2019 in London, UK