On June 22, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM) reported that AstraZeneca PLC ("AstraZeneca") and HUTCHMED’s savolitinib has been granted conditional approval in China for the treatment of patients with non-small cell lung cancer ("NSCLC") with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy (Press release, Hutchison China MediTech, JUN 22, 2021, View Source [SID1234586912]). This approval follows a priority review designation by China’s National Medical Products Administration ("NMPA") and marks the first regulatory approval globally for this oral, potent and selective MET tyrosine kinase inhibitor ("TKI").

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Approximately 2-3% of newly diagnosed NSCLC patients have MET exon 14 skipping alterations, a specific genetic mutation.

The approval by the NMPA was based on positive results from a Phase II trial conducted in China in patients with NSCLC with this mutation, including patients with the more aggressive pulmonary sarcomatoid carcinoma subtype. Savolitinib demonstrated effective anti-tumor activity based on an independent review of objective response rate ("ORR") and disease control rate ("DCR"). The approval is conditional upon successful completion of a confirmatory study in this patient population.

Christian Hogg, Chief Executive Officer of HUTCHMED, said: "It is with great pleasure that today we announce the first regulatory approval of savolitinib globally, HUTCHMED’s third self-discovered oncology drug to be commercialized. Our collaboration with AstraZeneca in 2011 has been an important driver in the development of this novel targeted oncology drug, involving both a China-based biotech and a global pharma company. This approval is a testament to the perseverance and scientific ingenuity of this long-standing alliance, and we are hopeful that this is only the beginning of the progress we can achieve for patients with MET-altered tumors."

Dave Fredrickson, Executive Vice President, Oncology Business Unit of AstraZeneca, said: "This approval makes savolitinib the only targeted medicine approved for these biomarker-selected patients in China, and it adds another novel medicine to our already diverse lung cancer portfolio. We are proud that this first-ever regulatory approval of savolitinib is in China, where we have a long-standing commitment to improving patient outcomes and working with the right partners to achieve that goal. Alongside HUTCHMED, we look forward to the continued development of this medicine across a range of cancers where MET alterations and amplification are drivers of tumor growth and treatment resistance."

About savolitinib
Savolitinib is an oral, potent and selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations).

Savolitinib is currently under development for multiple tumor types, including lung, kidney and gastric cancers, as a single treatment and in combination with other medicines.

HUTCHMED and AstraZeneca collaboration
In 2011, HUTCHMED and AstraZeneca entered a global licensing agreement with respect to the development and commercialization of savolitinib. HUTCHMED is responsible for the manufacturing and supply of savolitinib, and AstraZeneca is responsible for its commercialization in China and worldwide.

On June 22, 2021 Genmab A/S (Nasdaq: GMAB) reported that the European Commission (EC) has granted marketing authorization for the daratumumab subcutaneous (SC) formulation (daratumumab and hyaluronidase-fihj), known as DARZALEX SC in the European Union, in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd) for the treatment of adult patients with newly diagnosed systemic light-chain (AL) amyloidosis (Press release, Genmab, JUN 22, 2021, View Source [SID1234584224]). The EC also approved DARZALEX SC in combination with pomalidomide and dexamethasone (Pd) for the treatment of adult patients with multiple myeloma who have received one prior therapy containing a proteasome inhibitor (PI) and lenalidomide and were lenalidomide refractory, or who have received at least two prior therapies that included lenalidomide and a PI and have demonstrated disease progression on or after the last therapy. The approvals follow Positive Opinions by the CHMP of the European Medicines Agency in May 2021. In August 2012, Genmab granted Janssen Biotech, Inc. (Janssen) an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"AL amyloidosis is a potentially fatal blood disorder for which there is no cure, so we are extremely pleased that patients with AL amyloidosis in Europe may soon have a regimen including DARZALEX SC as a treatment option," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We are also pleased that, with the approval based on the APOLLO study, the combination of daratumumab with pomalidomide and dexamethasone will now be a treatment option for certain patients with relapsed or refractory multiple myeloma in Europe."

About the ANDROMEDA (AMY3001) study
The Phase 3 study (NCT03201965) included 416 patients newly diagnosed with AL amyloidosis. Patients were randomized to receive treatment with either daratumumab and hyaluronidase-fihj in combination with bortezomib (a proteasome inhibitor), cyclophosphamide (a chemotherapy), and dexamethasone (a corticosteroid) or treatment with VCd alone. The primary endpoint of the study was the percentage of patients who achieve hematologic complete response.

About the APOLLO (MMY3013) study
The Phase 3 (NCT03180736), randomized, open-label, multicenter study included 304 patients with multiple myeloma who have previously been treated with lenalidomide and a PI. Patients were randomized 1:1 to either receive daratumumab in combination with Pd or Pd alone. In the original design of the study, patients in the daratumumab plus Pd arm were treated with the intravenous (IV) formulation of daratumumab. As of Amendment 1 to the study protocol, all new subjects in the experimental arm were dosed with the SC formulation of daratumumab and patients who had already begun treatment with IV daratumumab had the option to switch to the SC formulation. The primary endpoint of the study was progression free survival (PFS). The study was conducted in Europe under an agreement between Janssen, the European Myeloma Network (EMN) and Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON).

About AL Amyloidosis
Amyloidosis is a disease that occurs when amyloid proteins, which are abnormal proteins, accumulate in tissues and organs. When the amyloid proteins cluster together, they form deposits that damage the tissues and organs. AL amyloidosis most frequently affects the heart, kidneys, liver, nervous system and digestive tract. There is currently no cure for AL amyloidosis or existing approved therapies for AL amyloidosis patients in Europe, though it can be treated with chemotherapy, dexamethasone, stem cell transplants and supportive therapies.1 It is estimated that in 2019 there were 4,388 diagnosed incident cases of AL amyloidosis in the five major European markets.2

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.3 Approximately 18,114 new patients were diagnosed with multiple myeloma and approximately 11,063 people died from the disease in the Western Europe in 2020.4 Globally, it was estimated that 176,404 people were diagnosed and 117,077 died from the disease in 2020.5 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.6

About DARZALEXSC (daratumumab and hyaluronidase-fihj)
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. DARZALEX SC (daratumumab and hyaluronidase-fihj) is the first subcutaneous CD38 antibody approved in the Europe for the treatment of both multiple myeloma and AL amyloidosis. 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). 7,8, 9, 10, 11

On June 22, 2021 4D pharma plc (AIM: DDDD, NASDAQ: LBPS), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs) – a novel class of drug derived from the microbiome, reported that Christophe Carite, Development Director, will deliver a presentation on 4D pharma’s strategy and capabilities for the manufacturing of its Live Biotherapeutic drug candidates at the upcoming virtual Microbiome Movement Drug Development Summit, on Thursday, July 1 at 2.15pm EDT (7.15pm BST) (Press release, 4d Pharma, JUN 22, 2021, View Source [SID1234584243]). He will also participate in a microbiome therapeutics manufacturing roundtable panel session.

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The presentation will discuss 4D pharma’s strategies, technologies and facilities to address the challenges of clinical-grade manufacturing and scale-up of its LBPs as a novel therapeutic modality for the treatment of a range of indications with unmet needs, including oncology, asthma, Parkinson’s disease and irritable bowel syndrome. The Company has successfully conducted the manufacturing optimization and scale-up of multiple novel LBPs at its in-house cGMP facility, and to date has progressed four candidates into clinical trials with additional candidates expected to enter the clinic in 2022.

In addition, Christophe Carite will join a panel entitled ‘Effectively scaling up microbiome manufacturing’. This roundtable will discuss the future of GMP infrastructure for microbiome therapeutics, the most effective quality control processes and potency methods, and the merits of developing internal manufacturing facilities or using CDMO partners.

As 4D pharma has led the development of LBPs it has built leading drug discovery and development expertise in this new field. The Company has also developed unparalleled know-how, processes and facilities for the manufacture of its LBPs to the highest regulatory standards. 4D pharma has fully cGMP-certified facilities in Europe, housing two 3,000L fermenters and downstream processing facilities with production capacity sufficient for late clinical and early commercial scale. Further, 4D pharma management were previously invited to contribute to the drafting of the European Pharmacopoeia’s quality standards for Live Biotherapeutic products which became effective in 2019.

"4D pharma’s unique expertise in the efficient, scalable and reproducible manufacturing of single strain LBPs has been invaluable in supporting rapid clinical and pre-clinical progress across our pipeline," said Christophe Carite, Development Director, 4D pharma. "Having these capabilities in-house not only supports and accelerates progress, but also generates valuable know-how, intellectual property and competitive advantage. As Live Biotherapeutics near commercialization, manufacturing is increasingly recognized as a critical factor in the future of this novel drug class, and 4D pharma is well positioned to successfully manage this important aspect of drug development in-house."

On June 22, 2021 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that the European Commission (EC) has granted the Janssen Pharmaceutical Companies of Johnson & Johnson two marketing authorizations for the subcutaneous formulation of daratumumab, known as DARZALEX SC in the European Union (Press release, Halozyme, JUN 22, 2021, View Source [SID1234584225]). The first authorization is for the use of DARZALEX SC in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd) for the treatment of adults with newly diagnosed systemic light-chain (AL) amyloidosis. The approval makes the DARZALEX SC based regimen the first approved therapy for AL amyloidosis in Europe. The second authorization is for the use of DARZALEX SC in combination with pomalidomide and dexamethasone (D-Pd) for the treatment of adults with multiple myeloma (MM) who have received one prior therapy containing a proteasome inhibitor and lenalidomide and were lenalidomide refractory, or who have received at least two prior therapies that included lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or after the last therapy.

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"We are pleased that Janssen received European Commission marketing authorizations for these important new indications," said Helen Torley, president and chief executive officer at Halozyme. "These authorizations will provide new treatment options for certain AL amyloidosis and multiple myeloma patients in Europe."

DARZALEX SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

On June 22, 2021 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug conjugates (ADCs) to treat hematological malignancies and solid tumors, reported that updated interim results from the ongoing pivotal Phase 2 clinical trial of camidanlumab tesirine (Cami) in patients with relapsed or refractory Hodgkin lymphoma were presented in an oral presentation (Abstract 075) at the 16th Annual International Conference on Malignant Lymphoma (ICML) (Press release, ADC Therapeutics, JUN 22, 2021, View Source [SID1234584244]). The pivotal Phase 2 study is intended to support the submission of a Biologics License Application.

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"The interim results from our ongoing pivotal Phase 2 trial of Cami as a single agent for patients with relapsed or refractory Hodgkin lymphoma demonstrate that a significant number of patients experience long-lasting treatment effects," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "In Phase 2, we used the optimal Phase 1 dosing schedule based on activity and tolerability, and we are encouraged by the interim data that show the median duration of response has not been reached. We also note that the incidence of GBS in Phase 2 is consistent with Phase 1. We look forward to providing future updates on this pivotal program as the overall response rate and duration of response data continue to mature."

Cami is being evaluated in a multicenter, open-label, single-arm Phase 2 clinical trial in 117 patients with relapsed or refractory Hodgkin lymphoma who have received ≥3 prior lines of treatment (≥2 lines if ineligible for hematopoietic stem cell transplantation, HSCT), including prior treatment with brentuximab vedotin and a checkpoint inhibitor. The interim data cut includes 101 evaluable patients who had been in the study a median of 5.1 months. Patients were heavily pretreated with a median of 6 prior lines of systemic therapy.

Key data presented at ICML by Pier Luigi Zinzani, MD, PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, Italy, include:

Overall response rate (ORR) was 66.3% (67/101 patients) with a complete response rate (CRR) of 27.7% and partial response rate (PRR) of 38.6%
Median duration of response has not been reached
No new safety signals have been identified and the most common grade ≥3 treatment-emergent adverse events in ≥5% of patients were hypophosphatemia (7.7%), maculopapular rash (6.8%), thrombocytopenia (6.8%), anemia (6.0%) and lymphopenia (6.0%)
To date, nine patients (7.7%) were able to proceed to HSCT following Cami treatment
7/117 patients (6.0%) developed Guillain-Barre syndrome/Polyradiculopathy (consistent with the incidence in the Phase 1 Hodgkin lymphoma patients)
"Patients with relapsed or refractory Hodgkin lymphoma who have failed several lines of previous therapy such as brentuximab vedotin and PD-1 blockade have limited treatment options," said Dr. Zinzani. "The antitumor activity and safety profile of Cami continues to demonstrate that this novel CD25-targeted ADC has the potential to address the unmet need in heavily pre-treated patients."

About Camidanlumab Tesirine (Cami)

Camidanlumab tesirine (Cami, formerly ADCT-301) is an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine. Once bound to a CD25-expressing cell, Cami is internalized into the cell where enzymes release the PBD-based payload, killing the cell. This applies to CD25-expressing tumor cells and also to CD25-expressing Tregs. The intra-tumoral release of its PBD payload may also cause bystander killing of neighboring tumor cells, and PBDs have also been shown to induce immunogenic cell death. All of these properties of Cami may enhance immune-mediated anti-tumor activity.

Cami is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma and a Phase 1b clinical trial as monotherapy and in combination with pembrolizumab in solid tumors.