On December 12, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported new data from the phase III FeDeriCa study which showed the investigational fixed-dose combination (FDC) of Perjeta (pertuzumab) and Herceptin (trastuzumab), administered by subcutaneous (SC) injection in combination with intravenous (IV) chemotherapy, demonstrated non-inferior levels of Perjeta in the blood (pharmacokinetics) and comparable efficacy and safety to standard IV infusions of Perjeta plus Herceptin and chemotherapy in eligible people with HER2-positive early breast cancer (eBC) (Press release, Hoffmann-La Roche, DEC 12, 2019, View Source [SID1234552293]). 1

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These new data, from a primary analysis of the FeDeriCa study, will be presented in a spotlight session at 07.00 CST today at the 2019 San Antonio Breast Cancer Symposium (SABCS) in Texas, US (Abstract #PD4-07).

SC administration of the FDC takes approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60 to150 minutes for subsequent maintenance infusions of the two medicines.2,3,4

"This fixed-dose subcutaneous combination has the potential to provide a quicker and less invasive method of administration for people with HER2-positive breast cancer being treated with Perjeta and Herceptin," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "This is the first time that we have brought together two of our targeted antibodies as a single subcutaneous injection that can be administered in just minutes."

The FeDeriCa study met its primary endpoint, with SC administration of the FDC showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough) when compared to IV administration of Perjeta. The geometric mean ratio (GMR; a type of average used when assessing pharmacokinetics) for the primary endpoint was 1.22 (90% CI: 1.14 to 1.31), with the lower limit of the 90% CI of the GMR=1.14≥0.80 (the pre-specified non-inferiority margin). A secondary endpoint of non-inferior Ctrough of Herceptin was also met, with blood concentrations for people receiving the FDC non-inferior to those receiving IV Herceptin (GMR=1.33 [90% CI: 1.24 to 1.43]; lower limit of 90% CI of GMR=1.24≥0.80). A non-inferiority endpoint was chosen for the study to ensure that people were receiving sufficient dosing with Perjeta and Herceptin as compared to the established IV doses at the same treatment intervals. In addition, rates of total pathological complete response (pCR), a secondary endpoint, were comparable between the treatment arms, with 59.7% of patients receiving the FDC and 59.5% of patients treated with IV Perjeta and Herceptin achieving a total pCR – a difference of 0.15% (95% CI: -8.67 to 8.97).1

The safety profile of the FDC in combination with chemotherapy was comparable to that of IV administration of Perjeta plus Herceptin and chemotherapy and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhoea and anaemia.1

In previous studies, SC administration has been shown to be strongly preferred by the majority of patients compared to IV administration of the same medicine, with the most common reason being that administration required less time in the clinic.5 Roche is currently investigating patient preference for SC administration of the FDC compared to standard IV administration of Perjeta and Herceptin in people with HER2-positive eBC in the PHranceSCa study. Interim results of this phase II study will be presented at a future medical meeting.

About the FeDeriCa study 6
FeDeriCa is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the pharmacokinetics, efficacy and safety of SC injection of the FDC of Perjeta and Herceptin in combination with chemotherapy, compared with standard IV infusions of Perjeta and Herceptin in combination with chemotherapy in 500 people with HER2-positive eBC who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings. The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and total pCR, meaning there is no tumour tissue detectable in the tissue removed at the time of surgery.

About the FDC of Perjeta and Herceptin
The FDC of Perjeta and Herceptin is a new SC formulation that combines Perjeta and Herceptin with Halozyme Therapeutics’ Enhanze drug delivery technology.

Trastuzumab in the FDC is the same monoclonal antibody as in IV Herceptin and pertuzumab in the FDC is the same monoclonal antibody as in IV Perjeta. The mechanisms of action of Perjeta and Herceptin are believed to complement each other as both bind to the HER2 receptor, but in different locations. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of the HER signaling pathways.7,8

The standard IV formulation of Perjeta in combination with IV Herceptin and chemotherapy (the Perjeta-based regimen) is approved in over 100 countries for the treatment of both early and metastatic HER2-positive breast cancer. In the neoadjuvant eBC setting, the Perjeta-based regimen has been shown to almost double the rate of pCR compared to Herceptin and chemotherapy.9 Additionally, the combination has been shown to significantly reduce the risk of recurrence of invasive disease or death in the adjuvant eBC setting.10 In the metastatic setting, the combination has shown an unprecedented survival benefit in previously untreated (first-line) patients with HER2-positive metastatic breast cancer.11

Halozyme’s Enhanze drug delivery technology may enable and optimise SC drug delivery for appropriate co-administered therapeutics. The technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body to aid in the dispersion and absorption of other injected therapeutic drugs.12

About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and metastatic HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.13 Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test which identifies people who will likely benefit from these medicines at the onset of their disease.

On December 12, 2019 Transgene (Paris:TNG) (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, reported that the primary endpoint (overall response rate) of the Phase 2 trial evaluating TG4010 in combination with chemotherapy and Opdivo (nivolumab) was not reached (Press release, Transgene, DEC 12, 2019, View Source [SID1234552318]). This combination regimen was assessed as a first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC) with low-to-no expression of PD-L1 by the tumor cells (PD-L1<50%). Transgene has taken the decision to stop further development of TG4010.
This multi-center single-arm Phase 2 trial enrolled 40 evaluable patients in the USA and Europe. It was conducted under a clinical collaboration agreement with Bristol-Myers Squibb, which is supplying nivolumab.

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Philippe Archinard, PhD, Chairman and CEO of Transgene, added:
"We are obviously very disappointed with the outcome of this Phase 2 trial which showed that the triple combination regimen of TG4010, chemotherapy and nivolumab did not sufficiently increase the response rate in this patient population with advanced NSCLC whose tumor express low or undetectable levels of PD-L1. Additional data analyses are still ongoing and the complete study results will be presented at an upcoming scientific conference.
With funding until 2022 and a diversified portfolio of novel immunotherapies targeting solid tumors, our strategy remains clear and unchanged. The Phase 2 combination trial of TG4001 in HPV-positive cancers is recruiting well and we expect to report the next clinical readout as planned in H1 2020. We are also advancing our two novel technology platforms myvac and Invir.IO. Clinical sites have been initiated and the first two trials evaluating TG4050, the first myvac candidate, will soon be enrolling patients. These trials will be jointly funded with NEC. A trial with TG6002 administered via the intrahepatic artery is also about to enroll its first patient. In addition, we expect to submit a clinical trial application in the first half of 2020 for BT-001, the first Invir.IO oncolytic virus encoding for an anti-CTLA4 antibody. Finally, our collaboration with AstraZeneca focused on generating novel multi-armed Invir.IO oncolytic viruses is making excellent progress.
These multiple advances give me great confidence that Transgene is well placed to demonstrate and deliver the potential of its novel therapeutic vaccines and oncolytic viruses designed to improve the treatment of solid tumors."

A conference call in English is scheduled on December 12, 2019, at 6:30 p.m. CET.

Webcast link to conference call: https://channel.royalcast.com/webcast/transgene/20191212_1/

Participant telephone numbers:

France: +33 (0) 1 7037 7166

United Kingdom: +44 (0) 20 3003 2666

United States: +1 212 999 6659

Confirmation code: Transgene

A replay of the call will be available on the Transgene website (www.transgene.fr) following the live event.

About TG4010
TG4010 is an immunotherapy that has been designed to express the coding sequences of the MUC1 tumor-associated antigen and the cytokine, Interleukin-2 (IL2). It is based on a modified Vaccinia virus (MVA) and has been shown to induce an immune response against MUC1 expressing tumors, such as non-small cell lung cancer (NSCLC). Its mechanism of action and safety profile make TG4010 a very suitable candidate for combinations with other therapies. The combination of TG4010 immunotherapy and chemotherapy has demonstrated significant efficacy in terms of progression-free survival and overall survival in patients with advanced stage NSCLC in a Phase 2b trial (Quoix et al. Lancet Oncol. 2015).

On December 12, 2019 Nordic Nanovector ASA (OSE: NANO) reported an update on its LYMRIT 37-05 Phase 1 trial of Betalutin in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who are not eligible for autologous stem cell transplantation (SCT) (Press release, Nordic Nanovector, DEC 12, 2019, View Source [SID1234552337]). DLBCL is an aggressive form of non-Hodgkin’s lymphoma (NHL) and accounts for up to 43% of all cases, making it the most common type of NHL.

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This open-label, dose-escalation safety trial is designed to assess the safety, tolerability, pharmacokinetic profile and preliminary anti-tumour activity of Betalutin in up to 24 patients. The primary goal of the trial is to identify the maximally tolerated dose of Betalutin which will then be further evaluated for safety and anti-tumour activity in an expansion cohort in order to select the recommended dose for phase 2. Three additional patients are currently being enrolled for further evaluation of the final dose cohort as one patient has experienced a reversible DLT (dose limiting toxicity).

On the three completed cohorts, no safety issues were identified. Evidence of disease control has been noted in some of the enrolled patients. We expect to complete the data read-out for the dose-escalation phase and submit the data to an international congress in 1H 2020.

Eduardo Bravo, Nordic Nanovector’s Chief Executive Officer, commented: "Patients with relapsed/refractory DLBCL who are not eligible for stem cell transplantation have very limited treatment options and a poor prognosis. As the safety profile of Betalutin will guide its potential for combination regimens as well as single agent consolidation therapy, we look forward to completing this part of the trial and proceeding with the expansion cohort."

On December 12, 2019 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that new data from the global phase III FeDeriCa study conducted by Genentech, a member of the Roche Group, will be presented today at the 2019 San Antonio Breast Cancer Symposium (SABCS) (Press release, Halozyme, DEC 12, 2019, View Source [SID1234552294]).

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The FeDeriCa study investigated a fixed-dose combination (FDC) of pertuzumab (Perjeta) and trastuzumab (Herceptin) for subcutaneous administration using Halozyme’s ENHANZE drug delivery technology in combination with intravenous (IV) chemotherapy.

The FeDeriCa study met its primary endpoint, with subcutaneous administration of the FDC showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough) when compared to IV administration of Perjeta. The geometric mean ratio (GMR; a type of average used when assessing pharmacokinetics) for the primary endpoint was 1.22 (90% CI: 1.14 to 1.31), with the lower limit of the 90% CI of the GMR=1.14≥0.80 (the pre-specified non-inferiority margin).(1)

A secondary endpoint of non-inferior Ctrough of Herceptin was also met, with blood concentrations for people receiving the FDC non-inferior to those receiving IV Herceptin (GMR=1.33 [90% CI: 1.24 to 1.43]; lower limit of 90% CI of GMR=1.24≥0.80). A non-inferiority endpoint was chosen for the study to ensure that people were receiving sufficient dosing with Perjeta and Herceptin as compared to the established IV doses at the same treatment intervals. In addition, rates of total pathological complete response (pCR), a secondary endpoint, were comparable between the treatment arms, with 59.7% of patients receiving the FDC and 59.5% of patients treated with IV Perjeta and Herceptin achieving a total pCR – a difference of 0.15% (95% CI: -8.67 to 8.97). (1)

The safety profile of the FDC in combination with chemotherapy was comparable to that of IV administration of Perjeta plus Herceptin and chemotherapy and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhea and anemia. (1)

"We are excited to see these more detailed results from the primary analysis of the FeDeriCa study presented at this important symposium," said Dr. Helen Torley, President and CEO. "We look forward to our partner beginning regulatory submissions in the near term so that patients suffering from HER2-positive breast cancer may have the option to receive Perjeta and Herceptin in a shorter administration time."

These new data from a primary analysis of the FeDeriCa study will be presented in a spotlight session at 7:00 AM CST today at the 2019 San Antonio Breast Cancer Symposium (SABCS) in Texas, US (Abstract #PD4-07).

Subcutaneous administration of the fixed-dose combination of Perjeta and Herceptin is approximately 8 minutes for the initial loading dose and approximately 5 minutes for each subsequent maintenance dose. Intravenous administration is approximately 150 minutes for the loading dose of Perjeta and Herceptin using standard IV formulations and between 60-150 minutes for subsequent maintenance infusions for the combination. (2,3,4)

About ENHANZE Technology
Halozyme’s proprietary ENHANZE drug-delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

On December 12, 2019 Molecular Partners AG (SIX:MOLN), a clinical-stage biotech company pioneering the use of DARPin therapeutics to treat serious diseases, reported the continued progress of its pipeline of proprietary therapeutic product candidates in oncology, as well as abicipar in ophthalmology (Press release, Molecular Partners, DEC 12, 2019, View Source [SID1234552322]).

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"We are very proud to present the progress of our company over this past year. We continue to see success of our DARPin platform, from its earliest inception, with abicipar, now on the verge of potential FDA approval, to the newest concepts of attacking previously unreachable targets in cancer, and beyond, with the emergence of our peptide-MHC platform. Our pipeline is set up to provide significant value for patients," said Patrick Amstutz, Ph.D., Chief Executive Officer of Molecular Partners. "Today we will hear from both world-class key opinion leaders as well as our own team highlighting our expertise in drug development and clinical execution and how we will continue to succeed into 2020 and beyond."

During its R&D Day in New York, entitled "Novel Therapeutic Designs Applied," the company will provide updates on its clinical and preclinical programs, including:

Abicipar:

Presentation of recently updated two-year results from CEDAR and SEQUOIA demonstrate that vision gains observed after one year with every 8-week and every 12-week dosing were maintained in the second year (presented at AAO 2019).
Abicipar sustained vision gains in year two with quarterly injections compared to monthly ranibizumab.
MP0250:

As stated at the 61st Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) last week, MP0250 continues to show long-lasting and deepening responses across a variety of patients with multiple myeloma in the relapsed/refractory setting. MP0250 has a novel mechanism of action, designed to target both VEGF and HGF. This design makes MP0250 ideally suited to attack the underlying disease and potentially improve sensitivity, or re-sensitize patients, to existing and emerging treatments.
The company also announced today its intent to evaluate partnering opportunities for MP0250. In conjunction with this endeavor, the company will not start the previously planned clinical trial investigating MP0250 in combination with an IMiD. This is aligned with the company’s corporate strategy to pursue combination data for the most relevant clinical combinations of MP0250, which would be more appropriately determined in collaboration with a partner.
"Given the dynamic landscape of current and emerging treatments for multiple myeloma, along with our strong data recently presented at ASH (Free ASH Whitepaper), we believe that aligning with a partner with an existing hematology franchise will be the best way to accelerate the MP0250 program through the clinic and into the treatment paradigm. In recent discussions with potential collaborators, it is obvious that the time for evaluating this opportunity is now," said Nicolas Leupin, M.D., MBA, Chief Medical Officer of Molecular Partners.

MP0274:

Also discussed today is MP0274, the second-most advanced DARPin drug candidate in the oncology pipeline. It has broad anti-HER activity, inhibiting HER1, HER2 and HER3-mediated downstream signaling via HER2, leading to induction of apoptosis.
The company continues to enroll patients and explore dosing in a phase 1 study.
Current dose levels are presently up to 8mg/kg, and initial data is anticipated in H1 2020.
MP0310 (AMG 506):

MP0310 is a multi-domain DARPin targeting FAP x 4-1BB, designed to activate immune cells specifically in the tumor and not in the rest of the body, potentially delivering greater efficacy with fewer side effects. Preclinical studies of MP0310 have demonstrated immune T-cell activation restricted to solid tumor tissues, and strong CD8 T-cell activation and expansion in vitro and in vivo.
The initial phase 1 study, being conducted by Molecular Partners, was initiated in mid-2019, and dose escalation is underway. Current clinical timelines are on track with initial data expected in H2 2020. In collaboration with Amgen, the clinical program is then expected to expand into additional combination cohorts, to be conducted by Amgen.
Beyond these clinical updates, the company will also detail its growing preclinical pipeline, including the data on FAP x CD40, now designated MP0317, a second multi-specific preclinical DARPin designed for localized activation. In addition to these updates, the company will highlight advances in the DARPin discovery platform, including the advent of peptide-MHC targeting and next-generation T-cell engagers.

In addition to an overview of the Molecular Partners clinical and preclinical pipeline, the R&D Day will feature presentations by the following experts:

Jeremy Wolfe, Practicing Ophthalmology Specialist
Stefan Knop, Department Head Hematology, University of Würzburg, Germany
Jordi Rodon, Associate Professor, Department of Investigational Cancer Therapeutics, MD Anderson Cancer Center
Logistics
The R&D Day for institutional investors, sell-side analysts, investment bankers, and business development professionals will take place at The Yale Club, 50 Vanderbilt Avenue, New York City, from 7:30 am – 10:00 am EST. To RSVP email Seth Lewis at [email protected].
Breakfast starts at 7:30 am EST. The presentations will begin at 8:00 am, followed by a Q&A session.

Audio webcast
The event will be webcast live and will be made available on the company’s website under the Investors section. The replay will be available for 90 days following the presentation.

Financial Calendar
February 6, 2020 Publication of Full-year Results 2019 (unaudited)
April 29, 2020 Annual General Meeting
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About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multi-specificity and multi-functionality. DARPin candidates can engage more than five targets, offering potential benefits over those offered by conventional monoclonal antibodies or other currently available protein therapeutics. The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields.

With their low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapeutics have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology and is advancing a proprietary pipeline of DARPin drug candidates in oncology and immuno-oncology. The most advanced global product candidate in partnership with Allergan is abicipar, a molecule for which phase 3 data have been filed to the respective regulators in both the US and in Europe. Several DARPin molecules for various ophthalmic indications are also in preclinical development. The most advanced DARPin therapeutic candidate wholly owned by Molecular Partners, MP0250, is in phase 2 clinical development for the treatment of hematological tumors. MP0274, the second-most advanced DARPin candidate owned by Molecular Partners, binds to Her2 and inhibits downstream signaling, which leads to induction of apoptosis. MP0274 is currently in phase 1. The company’s lead immuno-oncology product candidate MP0310 is a FAP x 4-1BB multi-DARPin therapeutic candidate designed to locally activate immune cells in the tumor by binding to FAP on tumor stromal cells (localizer) and co-stimulating T cells via 4-1BB (immune modulator). Molecular Partners has closed a collaboration agreement with Amgen for the exclusive clinical development and commercialization of MP0310. The molecule has entered in phase 1 of clinical development in H2 2019. Molecular Partners is also advancing a growing preclinical and research pipeline in immuno-oncology that features its "I/O toolbox" and additional development programs such as novel therapeutic designs to target peptide-MHC complexes. DARPin is a registered trademark owned by Molecular Partners AG.