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

On April 1, 2019 Replimune Group Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported that pre-clinical data on its oncolytic immunotherapy platform will be presented at a poster session today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held in Atlanta, Georgia (Press release, Replimune, APR 1, 2019, View Source [SID1234534884]).

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"The pre-clinical data to be presented in this poster reiterates the ability of our platform to provide a potent and versatile approach to developing new therapies intended to maximally activate a patient’s immune system against their own cancer," commented Robert Coffin, Ph.D., co-founder, President and CEO of Replimune. "This data supports the clinical development of our advancing pipeline of oncolytic immunotherapies, including our lead product candidate, RP1, and RP2 which additionally encodes an anti-CTLA-4 antibody."

Details of Replimune’s poster presentation:

Abstract Title: Development & characterization of a new oncolytic immunotherapy platform based on herpes simplex virus type 1 (Abstract #3136)

Session Date and Time: Monday April 1, 2019, 8:00AM – 12:00PM

Location: Georgia World Conference Center, Exhibit Hall B, Poster Section 22

The poster will be made available on the company’s website from the time of presentation.

Abstracts and full session details can be found at www.aacr.org

On April 1, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late stage biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported data from an investigation of the persistence and diversity of circulating T cells from metastatic melanoma patients from the innovaTIL-01 (C-144-01) study receiving lifileucel TIL therapy (Press release, Iovance Biotherapeutics, APR 1, 2019, View Source;p=irol-newsArticle&ID=2392939 [SID1234534832]). Results from an analysis of the persisting T cell clones circulating 42 days following infusion, as compared to the initial TIL product, demonstrated two phenomena: first, that TIL product from 100 percent of the evaluated patients in Cohort 2 of the innovaTIL-01 trial are persisting in circulation at 42 days post-infusion, and second, that each patient has a unique TIL product with almost no overlap between patients for expanding clones in the human body observed post-infusion. Furthermore, the small number of overlapping clones between a few patients were not associated with a clinical response. The uniqueness of the clonal profiles associated with response highlights the challenge of identifying a few T cell receptors as mediators of activity and supports using a polyclonal product such as the Iovance bulk TIL to treat high mutational load solid tumors.

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"Investigation of pharmacokinetics of lifileucel TIL in metastatic melanoma patients demonstrates excellent persistence of lifileucel 42 days post-infusion. In addition, the ability of lifileucel TIL therapy to generate responses in melanoma appears to be the result of each patient’s specific populations of their TIL product targeting the patient’s unique mutated tumor antigens" commented Maria Fardis, Ph.D., MBA, president and chief executive officer of Iovance. "The results of this study suggest that high mutational load solid tumors such as melanoma are unlikely to be effectively treated with products against a single or a small number of antigens, implying a potential need for a patient specific, polyclonal product such as Iovance’s TIL product lifileucel."

Identification of specific cancer-associated antigens responsible for an antitumor immune response continues to be an area of active research.1,2 The ability of autologous TIL therapy to respond to the unique cancer antigens present in each individual patient may be a factor in the response rates observed with lifileucel treatment.

Study results were detailed in a late-breaking poster presentation, "Persistence of cryopreserved tumor-infiltrating lymphocyte product lifileucel (LN-144) in C-144-01 study of advanced metastatic melanoma," at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2019 Annual Meeting. The presentation abstract and additional information is available on the AACR (Free AACR Whitepaper) conference website at View Source

Additional information about the registration-enabling innovaTIL-01 (C-144-01) study of lifileucel in advanced melanoma is available at View Source

Robbins PF, et al., Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nature Medicine. 2013 Jun;19(6):747-52. doi: 10.1038/nm.3161.
Lu YC, et al., Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions. Clinical Cancer Research. 2014 Jul 1;20(13):3401-10. doi: 10.1158/1078-0432.CCR-14-0433.

On April 1, 2019 Celgene Corporation (NASDAQ: CELG) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has expressed a positive opinion for the two triplets in basis of the IMiD of Celgene, REVLIMID (lenalidomide) and IMNOVID (pomalidomide) (Press release, Celgene, APR 1, 2019, View Source [SID1234534848]).

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The CHMP recommended the approval of the extension of the lenalidomide indication as combination therapy with bortezomib and dexamethasone (RVd) for the treatment of adult patients with newly diagnosed multiple myeloma not eligible for transplantation.

The Committee also recommended the approval of pomalidomide in combination with bortezomib and dexamethasone (PVd) for the treatment of adult patients with multiple myeloma who have received at least one previous lenalidomide treatment.

The final decision of the European Commission, which generally conforms to the CHMP’s recommendations, is expected in about two months.

" The CHMP’s positive opinion regarding the RVd and PVd triplets represents an important extension of therapy options for patients with multiple myeloma, both newly diagnosed and relapsed / refractory after previous treatment lines, " commented Michele Cavo , Full Professor of Hematology, University of Bologna and Director of the "Seràgnoli" Hematology Institute, S. Orsola-Malpighi University Hospital, Bologna – In fact, RVd is configured as a more effective therapeutic alternative with respect to the current standards of first-line treatment of patients who are not eligible to receive an autologous transplant, to which it ensures a significant prolongation both of overall survival (whose median value was higher than 6 years in the pivotal study) that of disease-free progression survival (median value greater than 40 months). Instead, PVd represents one of the most effective combinations currently available for the rescue therapy of relapsed or refractory patients after previous exposure to lenalidomide, and in particular to those who have become refractory to it.» .

The CHMP’s positive opinion for lenalidomide was based on data from SWOG S0777, a phase 3 study that evaluated the triplet with lenalidomide, bortezomib and dexamethasone (RVd) in adult patients with previously untreated multiple myeloma, not immediately eligible for ASCT 1 . The results of the study showed statistically significant improvements both in terms of progression-free survival (PFS) and overall survival (OS) in patients treated with RVd compared to those treated with lenalidomide plus dexamethasone (Rd). The choice of first-line treatment is important 2since over time patients respond less and less to therapy, manifesting increasingly shorter periods of remission in subsequent treatment lines. 3

The CHMP’s positive opinion for PVd was based on data from OPTIMISMM, the first prospective phase 3 study that evaluated the use of the triplet with pomalidomide in patients previously treated with lenalidomide who in most cases (70%) were found refractory to it. 4 This patient population represents a growing unmet medical need for which new therapeutic options are needed.

The OPTIMISMM results showed a significantly higher progression-free survival in patients treated with PVd compared to patients in the Vd treatment arm.

" The positive opinions of the CHMP for our combinations of IMiD RVd and PVd represent wonderful news for patients with multiple myeloma living in Europe, " says Nadim Ahmed , President of the Hematology / Oncology Division of Celgene. " We now hope that the EMA will approve these therapeutic options by making them available to patients, as our goal is to improve their outcomes at different stages of the disease ."

Lenalidomide in combination with bortezomib and dexamethasone, as well as pomalidomide in combination with bortezomib and dexamethasone, are currently not approved in any country.

Information on Celgene immunomodulatory drugs

IMiD agents are small molecules available as an oral therapy for the treatment of certain hematological malignancies owned exclusively by Celgene. It is hypothesized that they have multiple mechanisms of action. It has been observed that T cell activation and proliferation, IL-2 protein proliferation and CD8 + effector T cell activity are observed to increase. They also influence the stimulation and expression of natural killer cells(NK) acting within the cellular environment with the aim of inducing the immune system to attack cancer cells and at the same time directly attack them. In addition to the immunomodulatory properties, a tumoricidal and antiangiogenic activity is also hypothesized. Celgene IMiDs represent a mainstay of research on multiple myeloma with a growing number of studies in combination therapies in different disease settings.

Information on multiple myeloma

Multiple myeloma is a potentially fatal haematological neoplasm, which is characterized by tumor proliferation and suppression of the immune system. 5.6 It is a rare but lethal disease: every year, in Europe, there are 42,000 diagnoses, with about 26,000 deaths due to the disease. 7 The typical course of multiple myeloma includes periods of symptomatic disease alternating with periods of remission and, with time, appearance of refractoriness (non-responsiveness). 8

Information on the SWOG study S0777

SWOG S0777 is a multicenter, phase 3, randomized open trial, aimed at evaluating the efficacy and safety of RVd compared to Rd in the treatment of patients with previously untreated multiple myeloma for whom an autologous transplant of stem cells (ASCT). 1

In this study, 525 patients with newly diagnosed multiple myeloma (NDM) were enrolled with symptomatic and measurable disease aged 18 years or older. Patients were randomized (1: 1) to receive initial lenalidomide treatment with bortezomib and dexamethasone (RVd group) or lenalidomide and dexamethasone therapy only (group Rd). Randomization was stratified based on the ISS stage ( International Staging System, I, II or III ) and intention to transplant (yes vs.no). The RVd regimen was administered in eight cycles lasting 21 days. Bortezomib was administered at a dose of 1.3 mg / m by IV route on days 1, 4, 8 and 11, in combination with oral lenalidomide 25 mg / day on days 1-14 plus oral dexamethasone at a dose of 20 mg / day on days 1, 2, 4, 5, 8, 9, 11 and 12. The Rd regimen was administered in six cycles lasting 28 days. The Rd standard regimen consisted of 25 mg / day of lenalidomide orally on days 1-21 plus 40 mg / day of dexamethasone orally on days 1, 8, 15 and 22. 1

The results of the SWOG S0777 1 study showed a significant improvement in median progression-free survival (mPFS) in patients treated with RVd vs. Rd (42 vs. 30 months; HR 0.76, 95% CI 0.62-0.94; P = 0.01). A significant improvement in median overall survival with respect to Rd was also observed with RVd (89 vs. 67 months; HR 0.72, 95% CI 0.56-0.94; P = 0.013). The overall response and complete response rates were superior in patients treated with RVd compared to Rd (global response: 82% RVd vs 72% Rd; complete response: 16% RVd vs. 8% Rd). The safety of RVd was also in line with the consolidated safety profiles of each drug in the triplet. 9.10

Upon completion of the induction, all patients received continuous maintenance therapy with lenalidomide orally at 25 mg once a day for 21 days plus oral dexamethasone at a dose of 40 mg once a day on days 1 , 8, 15 and 22 of each cycle lasting 28 days. 1

Information on the OPTIMISMM study

OPTIMISMM is the first phase 3 comparative study on the safety and efficacy of PVd vs. Vd, as an early therapy line in patients with relapsed and refractory multiple myeloma (with 1-3 previous therapeutic regimens) and previous exposure to lenalidomide, including patients refractory to it. 4

This international, multi-center, phase 3, randomized, open-label study involved 559 patients (281 patients in the PVd arm and 278 in the Vd arm) with previous demographic, basal and pathological features generally well balanced between the two treatment arms . The median number of previous treatment lines was two, while over one third of patients had received a previous treatment line (40% in both treatment arms). All patients had previously been treated with lenalidomide: most were refractory to lenalidomide (71% in the PVd vs. arm69% in the Vd arm); last treatment refractoriness was observed in 70% and 66% of cases respectively. The median follow-up was 16 months. 4

The results of the OPTIMISMM study showed a significantly higher PFS in patients treated with PVd compared to patients in the Vd arm (11.20 vs. 7.10 months [P = <0.0001, HR 0.61; 95% CI: (0.49-0.77)]), with a 39% reduction in the risk of disease progression or death in the PVd arm. In an exploratory analysis on the subgroup of patients undergoing a previous treatment line, the median progression-free survival (mPFS) was 20.73 months with PVd vs.11.63 months with Vd (HR 0.54; p = 0.0027). In these patients, the benefit of PVd was independent of refractoriness or non-refractory to previous lenalidomide therapy. The safety of PVd was in line with the established safety profiles of each drug in the triplet. 7.11

Patients were stratified according to the following criteria: age (≤75 years vs. > 75 years), number of previous therapeutic regimens for myeloma (1 vs. > 1) and β2-microglobulin levels (from <3.5 mg / L vs. ≥ 3.5 to ≤ 5.5 mg / L vs.> 5.5 mg / L). Patients were randomized 1: 1 to receive PVd or Vd. In 21-day cycles, patients received pomalidomide 4 mg / day on days 1-14 (PVd arm only); bortezomib 1.3 mg / m2 on days 1, 4, 8 and 11 of cycles 1-8 and on days 1 and 8 of cycle 9 and subsequent; and dexamethasone 20 mg / day (10 mg if age was> 75 years) on days when treatment with bortezomib was expected and on subsequent days. 4

Information on REVLIMID (lenalidomide)

Lenalidomide is approved in Europe as a monotherapy and is indicated for the maintenance therapy of adult patients with newly diagnosed multiple myeloma who have undergone an autologous stem cell transplant. Lenalidomide as a combination therapy is approved in Europe, the United States, Japan and about 25 other countries for the treatment of adult patients with multiple previously treated myeloma (MM) who are not eligible for transplantation. It is also approved in association with dexamethasone for the treatment of patients with MM who have received at least one previous therapy in almost 70 countries in Europe, the Americas, the Middle East and Asia

Lenalidomide is also approved in the United States, Canada, Switzerland, Australia, New Zealand and in several Latin American countries, as well as in Malaysia and Israel, for the treatment of transfusion-dependent anemia due to myelodysplastic syndromes (MDS) to low or intermediate-1 risk, associated with an isolated cytogenetic abnormality with deletion of 5q, with or without further cytogenetic abnormalities, as well as in Europe for the treatment of patients with transfusion-dependent anemia due to low or intermediate-1 myelodysplastic syndromes , associated with an isolated cytogenetic abnormality with deletion of 5q, in cases where other therapeutic options have proved insufficient or inadequate.

It is also approved in Europe and the United States for the treatment of patients with relapsed or refractory mantle lymphoma (MCL) after two previous therapies, one of which includes bortezomib. In Switzerland, Lenalidomide is indicated for the treatment of patients with relapsed or refractory MCL after previous therapy with bortezomib and chemotherapy / rituximab.

Lenalidomide is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical studies.

About IMNOVID (pomalidomide)

Pomalidomide administered in combination with dexamethasone is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have undergone at least two previous therapies, including both lenalidomide and bortezomib and with demonstrated progression of the disease during the last therapy. It belongs to the class of so-called immunomodulatory drugs (IMiD ).

Pomalidomide was initially approved in the United States in 2013 in association with dexamethasone for the treatment of patients with multiple myeloma who received at least two previous therapies including lenalidomide and a proteasome inhibitor and with demonstrated progression of the disease during or within 60 days of completion of the latest therapy.

In 2013 it was approved in the EU, in association with dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma, who underwent at least two previous therapies, including both lenalidomide and bortezomib and with demonstrated progression of the disease during the last therapy.

It is also approved in a total of 66 countries in the world, including Australia, Canada, Japan and Switzerland, for use in association with dexamethasone for indications similar to those approved in the United States and the EU.

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.