On February 25, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported topline results from the Phase III COLUMBA study (MMY3012) of subcutaneous (SC) versus intravenous (IV) daratumumab for patients with relapsed or refractory multiple myeloma (Press release, Genmab, FEB 25, 2019, View Source [SID1234533635]). The results showed that SC administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 is non-inferior to IV administration of daratumumab with regard to the co-primary end points of overall response rate (ORR) and Maximum Trough concentration (Ctrough) of daratumumab on day 1 of the third treatment cycle.

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!

The ORR for patients treated with SC daratumumab was 41.1% (n=263) versus 37.1% in patients treated with IV daratumumab (n= 259). The lower limit of the 95% Confidence Interval (CI) for the ratio of the two met the specified non-inferiority criterion for this co-primary endpoint. The geometric mean of Ctrough for patients treated with SC daratumumab was 499 mg/mL (n=149) versus 463 mg/mL in patients treated with IV daratumumab (n= 146). The lower limit of the 95% CI for the ratio of the two met the specified non-inferiority criterion for this co-primary endpoint.

No new safety signals were detected and Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, will discuss the potential for a regulatory submission for this formulation with health authorities, and plans to submit the data to an upcoming medical conference and for publication in a peer-reviewed journal.

"With the data from each of the key clinical studies we learn more about the difference that daratumumab potentially can make to the lives of patients suffering with multiple myeloma. I am particularly excited about the results from this study as it may support a much quicker and far more convenient administration of daratumumab, which would provide an important benefit for many patients and their families," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the COLUMBA (MMY3012) study
The Phase III trial (NCT03277105) is a randomized, open-label, parallel assignment study that includes 522 adults diagnosed with relapsed and refractory multiple myeloma. Patients were randomized to receive either: SC daratumumab, as 1800 mg daratumumab with rHuPH20 2000 U/mL once weekly in Cycle 1 and 2, every two weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study or 16 mg/kg IV daratumumab once weekly in Cycle 1 and 2, every two weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The co-primary endpoints of the study are ORR and Maximum trough of daratumumab (Ctrough; defined as the serum pre dose concentration of daratumumab on Cycle 3 Day 1).

About DARZALEX(daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

On February 25, 2019 Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical company focused on the development of novel products for serious rare and ultra-rare genetic diseases, reported that it has commenced an underwritten public offering of up to $250,000,000 of shares of its common stock (Press release, Ultragenyx Pharmaceutical, FEB 25, 2019, View Source [SID1234533671]). In addition, the company is expected to grant the underwriters of the offering an option for a period of 30 days to purchase up to an additional $37,500,000 of shares of common stock at the public offering price, less the underwriting discount.

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!

The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed. J.P. Morgan Securities LLC, Goldman Sachs & Co. LLC, BofA Merrill Lynch and Cowen are acting as joint book-running managers for the offering.

A registration statement relating to these securities has been filed with the Securities and Exchange Commission and became automatically effective on February 21, 2018. This offering is being made solely by means of prospectus supplement and accompanying prospectus. When available, copies of the preliminary prospectus supplement and the accompanying prospectus related to the offering may be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at 866-803-9204, or by email at [email protected]; Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, facsimile: 212-902-9316 or by emailing [email protected]; BofA Merrill Lynch, NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, NC 28255-0001, Attention: Prospectus Department, or by email at [email protected]; and Cowen, c/o Broadridge Financial Services, 1155 Long Island Avenue, Edgewood, NY, 11717, United States, Attn.: Prospectus Department or by telephone 1-631-274-2806.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On February 15, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported its financial and operational results for the transition period from October 1 to December 31, 2018 (Press release, Autolus, FEB 25, 2019, View Source [SID1234533705]). On December 19, 2018, the board of directors approved a change of fiscal year end from September 30 to December 31. The Company has also filed a report on Form 20-F with the Securities and Exchange Commission for the transition period.

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!

Key recent 2019 events and 2018 highlights include:

Clinical

In February 2019, Autolus announced updated data from the ongoing Phase 1 CARPALL trial of AUTO1 in pediatric patients with relapsed/refractory acute lymphoblastic leukemia (pALL) at the European Hematology Association (EHA) (Free EHA Whitepaper) 1st European CAR T Cell Meeting held in Paris, France. Consistent with the original presentation at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, the emerging safety profile appears to be manageable and differentiated. Notably, none of the patients experienced severe cytokine release syndrome (CRS) (Grade 3-5) and none of the patients required treatment with tociluzumab or steroids. Thirteen patients experienced CRS at Grade 1 or 2. As previously reported, one patient experienced Grade 4 neurotoxicity; there were no other reports of severe neurotoxicity (Grade 3-5). Eleven patients experienced cytopenia that was not resolved by day 28 or recurring after day 28 (Grades 1-4). Two patients developed significant infections, and 1 patient died from sepsis while in molecular complete response (CR). In the trial, AUTO1 combined a high molecular complete response rate (86% after a single dose of AUTO1) with robust persistence at one year follow-up in pediatric acute B cell leukemia patients. The median duration of remission in responding patients was 7.3 months with a median follow-up of 14 months. Event-free survival was 46% with overall survival of 63% at 12 months.

In December 2018, Autolus announced preliminary results from the ongoing Phase 1/2 AMELIA clinical trial of AUTO3 in patients with relapsed/refractory pediatric acute lymphoblastic leukemia (pALL) at the 60th ASH (Free ASH Whitepaper) Annual Meeting in San Diego, California. Researchers reported on ten patients with relapsed or refractory pALL who received an

AUTO3 infusion as a single dose or split dose dependent on their tumor burden. It was observed that AUTO3 was generally well-tolerated with no severe CRS and only one case of Grade 3 neurotoxicity observed, which was considered unlikely related to AUTO3 and primarily attributed to prior intrathecal chemotherapy. Eight out of ten patients achieved minimal residual disease-(MRD) negative CR and higher response rates were observed at doses ³3 x 106/kg dose levels with all patients achieving MRD-negative remission. In the higher dose group, four out of six patients had an ongoing molecular CR as of the cutoff date and, importantly, no loss of CD19 or CD22 was noted among the relapsed patients.

At the 60th ASH (Free ASH Whitepaper) Annual Meeting in December 2018, Autolus also announced preliminary results of the ongoing Phase 1/2 ALEXANDER clinical trial of AUTO3 in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The principal investigator reported that AUTO3 followed by consolidation with a limited duration of anti-PD1 therapy appeared to have a manageable safety profile at the doses evaluated. Out of the seven patients evaluable for safety, none developed CRS grade 3 or higher and one patient had Grade 3 neurotoxicity, considered possibly related to AUTO3. No dose limiting toxicities were observed and dose escalation continues. Six patients were evaluable for response; two patients achieved a CR (which was ongoing at six and three months post-treatment, respectively) and two patients had a partial response; two patients did not respond.

In December 2018, Autolus announced an update on its novel CAR T cell program for peripheral T cell lymphoma. The first patient was dosed in the Phase 1/2 LibrA T1 clinical trial of AUTO4, a developmental therapy for the treatment of relapsed or refractory TRBC1-positive peripheral T cell lymphoma (PTCL). Also, the preclinical data from the sister program AUTO5, targeting TRBC2-positive lymphoma, were presented at the 60th ASH (Free ASH Whitepaper) Annual Meeting.

Autolus will host an R&D Day in New York City on March 26, 2019 for the investment community. This event will provide an update on Autolus’ current clinical programs and highlight the company’s next-generation programed T cell products for hematological and solid tumor indications.

Manufacturing and Product Delivery

In February 2019, the Medicines and Healthcare Products Regulatory Agency approved an extension to the GMP license of the Cell and Gene Therapy Catapult Manufacturing Centre in Stevenage, which, with its innovative operational and licensing model, enables Autolus to manufacture clinical trial supply from this facility.

In January 2019, Autolus announced it has signed a long-term, full-building lease with Alexandria Real Estate Equities, Inc. for the construction and development of an 85,000 square foot build-to-suit facility to be located in the Shady Grove Life Sciences Center in

Rockville, Maryland. The new facility will house offices for Autolus’ U.S.-based research and development, commercial and corporate functions and serve as its first full commercial-scale manufacturing center, with a planned capacity of producing 5,000 T cell therapies annually.

Also in January, Autolus initiated the build-out of a manufacturing facility in Enfield, U.K. The facility is planned to open in 2020 and will provide global supply of viral vector as well as a planned capacity of 1,000 T cell therapies annually.

Autolus is establishing a series of intelligent systems to efficiently manage all aspects of manufacture and certification of supply. Costs will be partly covered through a grant from Innovate UK. To date, Autolus has been awarded Innovate UK grants totaling £6.7 million (approximately $8.6 million).

Corporate Highlights

In December 2018, Autolus announced that it had been selected for addition to the NASDAQ Biotechnology Index (Nasdaq: NBI) as part of the annual re-ranking.

Autolus strengthened its management and board during 2018. Key company management appointments included Andrew J. Oakley as senior vice president and chief financial officer and Adam Hacker, PhD as senior vice president for regulatory affairs and quality. Key board of directors appointments included Linda Bain, current chief financial officer of Codiak BioSciences, Inc., and Cynthia M. Butitta, former chief operating officer of Kite Pharma.

In June 2018, Autolus completed a U.S. initial public offering of American Depositary Shares, representing a total of 10,147,059 ordinary shares, including full exercise of the underwriters’ over-allotment, for net proceeds, after deducting underwriting discounts and commissions and offering expenses, of $156.5 million.

"In 2019, we expect significant progress that will build on the momentum of last year," stated Dr. Christian Itin, chairman and chief executive officer of Autolus. "Our robust pipeline of clinical and pre-clinical programs is progressing well, and we expect to move two programs into registrational trials and provide updates on all of our active programs at conferences during the course of this year. The next scheduled data presentation will be for AUTO1 in adult acute lymphoblastic leukemia at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Annual Meeting in April."

Financial results for the period from October 1 through December 31, 2018:

As stated above, we are transitioning to reporting our results on a calendar year basis, starting with the fiscal year ended December 31, 2018, and as such we are presenting audited results for the three-month period from October 1, 2018 to December 31, 2018, and the comparative period for 2017 discussed below, which is unaudited.

Cash and equivalents at December 31, 2018 totaled $217.5 million, compared with $129.0 million at December 31, 2017, due primarily to the $156.5 million in net proceeds resulting from Autolus’ U.S. initial public offering, which closed in June 2018.

Net total operating expenses for the three months ended December 31, 2018 were $25.0 million, net of grant income of $0.3 million, as compared to net operating expenses of $8.4 million, net of grant income of $0.2 million, for the same period in 2017. The increase in expenses was due, in general, to the increase in clinical trial activity, which is expected to deliver on key milestones in 2019; increased headcount; and the cost of being a public company.

Research and development expenses increased to $17.7 million for the three months ended December 31, 2018 from $5.6 million for the three months ended December 31, 2017. Cash costs, which exclude depreciation as well as share-based compensation, increased to $15.2 million from $5.1 million. The increase in research and development cash costs of $10.1 million consisted primarily of an increase of $4.3 million in project expenses related to the activities necessary to prepare, activate, and monitor clinical trial programs, an increase in compensation-related costs of $3.8 million primarily due to an increase in headcount to support the advancement of our product candidates in clinical development, and an increase of $2.0 million in facilities costs and consumables supporting the expansion of our research and translational science capability and investment in manufacturing facilities and equipment.

General and administrative expenses increased to $7.6 million for the three months ended December 31, 2018 from $3.1 million for the three months ended December 31, 2017. Cash costs, which exclude depreciation as well as share-based compensation, increased to $5.7 million from $2.5 million. The increase of $3.2 million consisted primarily of an increase of $2.3 million in insurance, patent costs, commercial costs, investor relations and communication costs and additional facility costs, as well as an increase in compensation-related expense of $0.9 million.

Net loss attributable to ordinary shareholders was $20.6 million for the three months ended December 31, 2018, compared to $7.5 million for the same period in 2017.

The basic and diluted net loss per ordinary share for the three months ended December 31, 2018 totaled $(0.52) compared to a basic and diluted net loss per ordinary share of $(0.26) for the three months ended December 31, 2017.

Autolus anticipates that cash on hand provides a runway into calendar year 2021.

Conference Call and Presentation Information

Autolus management will host a conference call today, February 25, at 8:00 a.m. EST/ 1:00pm GMT to discuss the company’s financial results and operational update.

To listen to the webcast and view the accompanying slide presentation, please go to: View Source

The call may also be accessed by dialing 877-270-2148 (U.S.) and 412-902-6510 (international) and asking the operator to join the Autolus Therapeutics conference call. After the conference call, a replay will be available for one week. To access the replay, please dial 877-344-7529 (U.S.) or 412-317-0088 (international) and enter replay access code 10129000.

On February 25, 2019 Magenta Therapeutics (NASDAQ:MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, reported that the Company highlighted preclinical research on its targeted conditioning programs in four presentations and posters at the Transplant and Cellular Therapy (TCT) annual meeting (Press release, Magenta Therapeutics, FEB 25, 2019, View Source [SID1234533636]).

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!

Patients currently undergoing stem cell transplant or stem cell gene therapy are first prepared, or conditioned, with non-specific, genotoxic chemotherapy alone or in combination with total body irradiation. This process is associated with significant side effects, including infertility and mortality risks, which can prevent many eligible patients from undergoing a stem cell transplant or gene therapy. Magenta is developing a portfolio of targeted antibody drug conjugates (ADCs), including non-genotoxic agents, that selectively remove the specific cells needed to enable a successful transplant or gene therapy procedure without the toxicities of chemotherapy and radiation. Magenta’s C100 program targets CD45, expressed on both stem and immune cells, with the goal of enabling stem cell transplant in blood cancer and autoimmune diseases. Magenta’s C200 program targets CD117, expressed on stem cells, with potential applicability as a conditioning agent before gene therapy for genetic diseases and stem cell transplant for blood cancers.

"Stem cell transplant and gene therapy are potential cures for many diseases, including sickle cell disease, blood cancers, and autoimmune diseases, such as multiple sclerosis and systemic sclerosis. However, the toxicity of the current conditioning regimens prevents a significant percentage of patients from considering a transplant or gene therapy and requires the patients who do undergo the procedure to trade their disease for the prospect of infertility, organ damage, secondary cancers and even death," said Michael Cooke, Ph.D., Chief Scientific Officer, Magenta Therapeutics. "Data in non-human primates from Magenta’s two distinct lead conditioning programs show potent and selective depletion of the target cells, and the ADCs were well tolerated. Based on these promising data, we selected a development candidate for the C200 program and have moved into IND-enabling studies. We expect to declare a candidate for the C100 program this year and move into IND-enabling studies in 2020."

Non-Genotoxic Conditioning Using Amanitin Antibody-Drug Conjugates Targeting CD45 Effectively Deplete Human and Non-Human Primate Hematopoietic Stem Cells and Immune Cells (C100 Program)

Key results, presented by Rahul Palchaudhuri, Ph.D., Magenta Therapeutics:

A single dose of an anti-CD45 ADC achieved efficient depletion of immune cells in the periphery and hematopoietic stem cells in the bone marrow in preclinical models.
An anti-CD45 amanitin ADC with engineered fast half-life demonstrated potent depletion of peripheral immune cells as well as immune cells and hematopoietic stem cells in the bone marrow of non-human primates.
An anti-CD45 amanitin ADC with engineered fast half-life demonstrated potent stem and immune cell depletion and rapid clearance, providing optimal pharmacokinetics for patient preparation for stem cell transplant.
These ADCs were well tolerated at the efficacious doses.
Simultaneous depletion of immune and hematopoietic stem cells using an anti-CD45 ADC with rapid clearance may enable safer conditioning for allogeneic transplant and enable an immune-reset in autoimmune disease transplantation, broadening patient access to this potentially curative therapy.
Magenta plans to optimize the anti-CD45 ADC and select a development candidate in 2019, with IND-enabling studies to begin in 2020.
Magenta is testing anti-CD45 ADCs in preclinical models of autoimmune disease, with data expected later in 2019.
A CD117-Amanitin Antibody Drug Conjugate Effectively Depletes Human and Non-Human Primate Hematopoietic Stem and Progenitor Cells: Targeted Non-Genotoxic Conditioning for Bone Marrow Transplant (C200 Program)

Key results, presented by Brad Pearse, Ph.D., Magenta Therapeutics:

An anti-CD117 ADC conjugated with amanitin potently depleted both human and non-human primate hematopoietic stem cells and progenitors in vivo.
An anti-CD117 amanitin ADC with engineered fast half-life demonstrated potent stem cell depletion and rapid clearance, representing optimal pharmacokinetics and pharmacodynamics for patient preparation for stem cell transplant or gene therapy.
The ADCs were well tolerated at the efficacious doses.
Potent and selective depletion of stem cells with rapid clearance of the ADC has the potential to provide a significant improvement over current approaches to patient preparation prior to stem cell transplant and gene therapies, broadening patient access to curative therapies.
Magenta has declared a lead for development for the C200 program and moved into IND-enabling studies.
Magenta is undertaking studies of C200 in preclinical models for gene therapy conditioning, with data expected later this year.
Single Doses of Antibody Drug Conjugates (ADCs) Targeted to CD117 or CD45 Have Potent In Vivo Anti-Leukemia Activity and Survival Benefit in Patient-Derived AML Models

Key results, presented by Jennifer Proctor, Magenta Therapeutics:

CD117 is expressed on human hematopoietic stem and progenitor cells and on leukemia cells in 80% of patients with acute myeloid leukemia (AML) and in 65% of patients with myelodysplastic syndromes (MDS); CD45 is expressed on all lympho-hematopoietic cells in many blood cancers.
Both the anti-CD117 amanitin ADC and the anti-CD45 amanitin ADC demonstrated potent killing of human hematopoietic stem cells and leukemia cell lines in vitro.
A single dose of either ADC demonstrated potent in vivo anti-leukemia activity in mice bearing established human leukemia cell lines.
Both ADCs significantly improved the survival of mice engrafted with human leukemia cells from AML patients, which included leukemias that were resistant to multiple lines of therapy.
Magenta Therapeutics’ C200 and C100 programs are designed with the dual intent of selectively eliminating the necessary cells to enable a successful transplant and reducing disease burden.
Magenta continues to progress ADC-based conditioning approaches targeting CD45 and CD117 toward the clinic.
CD45-Targeted Antibody-Drug Conjugate Plus Post-Transplant Cytoxan is Sufficient to Enable Allogeneic Bone Marrow Transplant in a Minor Mismatch Mouse Model (C100 Program)

Key results, presented by Sharon Hyzy, M.S., Magenta Therapeutics:

ADCs targeted to mouse CD45 have been shown to effectively condition immunocompetent mice for autologous stem cell transplant.
To investigate the utility of a murine-specific tool ADC conjugated to saporin to enable allogenic transplant, Magenta assessed this ADC as a single agent or in combination with immunosuppressive agents to facilitate transplant in a murine allogeneic transplant model.
A single dose of anti-CD45 saporin ADC, when combined with post-transplant cyclophosphamide to prevent graft-versus-host-disease, enabled successful engraftment across minor histocompatibility antigens.
The anti-CD45 saporin ADC was more effective than an unconjugated anti-CD45 antibody, pre-transplant cyclophosphamide, or sublethal irradiation in combination with post-transplant cyclophosphamide.
Magenta continues to investigate additional linker-toxins as well as ADC-based conditioning in multiple allogeneic mouse models.

On February 25, 2019 Exicure, Inc. (OTCQB: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) constructs, reported that it has dosed the first patient in its multicenter, open-label, Phase 1b/2 study of AST-008 combined with pembrolizumab (Press release, Exicure, FEB 25, 2019, View Source;p=RssLanding&cat=news&id=2388720 [SID1234533672]). Enrollment in the trial is open to patients with superficial injectable tumors in advanced or metastatic solid tumor conditions including Merkel cell carcinoma, head and neck squamous cell carcinoma, cutaneous squamous cell carcinoma and melanoma. clinicaltrials.gov NCT03684785

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!

"We believe that combining our immune system agonist drug with checkpoint inhibitors is an important strategy for leveraging the patient’s own immune system to fight cancer. We are excited to bring this approach into cancers like Merkel cell carcinoma, where patients have limited success using currently available treatments," said Exicure CEO Dr. David Giljohann. "It is also an important milestone for Exicure in the development of our platform technology, which allows us to digitally design drug candidates and potentially bring them into clinic faster."

The primary objective of the Phase 1b dose escalation stage is to assess the safety and tolerability of Exicure’s AST-008 drug alone and in combination with pembrolizumab, and to determine a dose for the Phase 2 stage of the study. Patients in the dose escalation stage may have previously been exposed to antibody checkpoint inhibitors, but not as a requirement for inclusion in the trial. In the Phase 2 portion of the study, Exicure will further evaluate AST-008 in combination with pembrolizumab in patients who have previously received but not responded to anti-PD-1 or anti-PD-L1 antibody therapy.

About Exicure’s AST-008 Drug

AST-008 is a toll-like receptor nine (TLR9) agonist oligonucleotide in a proprietary SNA format with immune-stimulatory properties. SNAs are dense, radial arrangements of nucleic acids (DNA) that have high cellular uptake and an enhanced presentation of the DNA for TLR9 agonism. AST-008 is designed to enter into and activate immune cells to elicit an immune response to treat solid tumors in combination with other agents such as checkpoint inhibitors. We observed that AST-008 showed potent antitumor activity as a monotherapy and synergized with anti-PD-1 antibodies in multiple preclinical tumor models. In a successful Phase 1 trial in healthy volunteers, AST-008 activated key immune cells and cytokines predictive for an anti-tumor effect in patients.