The company founded by Professor Rao Yi chose hemophilia A, and another AAV gene therapy passed the approval of Yimai Meng

January 4, 2022 / eMedClub News/--Recently, the official website of the government service platform of the Ministry of Science and Technology shows that the first batch of approval results for the administrative licensing of human genetic resources in China in 2022 has been released
.

One of the approved projects is titled "Clinical exploration of adeno-associated virus (AAV) vector expressing human coagulation factor VIII gene therapy technology for the treatment of hemophilia A"
.

The clinical trial will be carried out in the Hematology Hospital of the Chinese Academy of Medical Sciences, sponsored by Suzhou Huayi Lejian Biotechnology Co.
, Ltd.
, and is an investigator-initiated clinical study (IIT)
.
About Suzhou Huayi Lejian Suzhou Huayi Lejian has changed its name several times with the development of the company .

Previous names include: Beijing Yuanji Quality, Beijing Huayi Lejian and Suzhou Huayi Liangjian Biotechnology Co.
, Ltd.
Its main holding company is Beijing Yuanji Huayi, with Rao Yi as its chairman .
In 2019, Rao Yi set up the company in Beijing as a scientific founder, focusing on the research and development of gene therapy products.
The initial capital injection of Huaxing Capital and Tencent was 20 million .
In 2020, Huayi Lejian announced that it had successfully built a production system for AAV suspension cells and completed the preclinical POC of some pipelines .
At the end of 2020, after completing the 80 million pre-A round of financing, the company will advance the pilot line to the exploratory clinical trial stage and move to Suzhou Biopark in May 2021 .
At present, the company has started the construction of an 8,600-square-meter office and GMP production base in the third phase of the Suzhou Industrial Park Biomedical Industrial Park .Its main pipeline is in the field of liver-targeted gene therapy, such as hemophilia
A.

An IND application to the NMPA is expected to be submitted in the second half of 2022, with a view to launching a Phase 1 clinical trial in 2023
.

This time, IIT is also advancing its product candidates into the next stage ahead of schedule
.

About Investigator-Initiated Clinical Research (IIT) Investigator-initiated clinical research is a form of research that exists widely in the pharmaceutical industry at home and abroad.
It is called an investigator initiated trial (IIT).
As one of the types of post-marketing clinical research, it refers to Clinical research on marketed drugs, medical devices or diagnostic reagents initiated by an investigator (mainly referring to a clinician)
.

The scope of its research is often in areas not covered by industry-sponsored trials (IST) sponsored by pharmaceutical companies, such as rare disease research, comparison of diagnosis or treatment methods, and new uses of marketed drugs
.

The clinical research initiated by researchers and the clinical research initiated by pharmaceutical companies are parallel and complementary to each other, so as to better promote the depth and breadth of drug research, obtain more research data, and provide evidence-based medicine
.

Development and Challenges of AAV Gene Therapy for Hemophilia A In the field of AAV gene therapy, hemophilia is one of the hottest tracks
.

In recent years, due to advances in gene therapy and protein engineering, gene therapy has achieved significant breakthroughs in the clinical application of hemophilia, and the drug market for hemophilia is undergoing major changes
.

According to a report published by Coherent Market Insights, the hemophilia gene therapy market is estimated to exceed USD 780 million in 2026, with a compound annual growth rate (CAGR) from 2018 to 2026 or as high as 56.
0%
.

Compared with hemophilia B, the incidence of hemophilia A is about 4 times that of hemophilia B, and the market prospect is broad
.

The original mutant gene of hemophilia A is very large, exceeding the packaging limit of the AAV vector.
Therefore, after 15 years of hard work, researchers successfully cut out the unnecessary part of the gene, and since then brought hemophilia A.
The development of gene therapy for disease
.

In addition, the persistence and one-time administration of AAV gene therapy has also plagued hemophilia treatment
.

In 2020, Pfizer/Sangamo announced progress data for its gene therapy giroctocogene fitelparvovec (SB-525 or PF-07055480) showing significant reductions in factor VIII levels over time after administration to individual patients
.

What's more, the marketing application of BioMarin's hemophilia A gene therapy valoctocogene roxaparvovec (hereinafter referred to as: valrox) was rejected by the FDA because it did not submit sufficient follow-up data to prove the durability of its efficacy
.

Gene therapy for hemophilia A leads the pack.
However, at present, this problem has been substantively proved, and valrox has become the fastest-growing hemophilia A drug
.

In the past six months, the gene therapy for hemophilia A has released many updates
.

AAV Gene Therapy ➤ BioMarin's valoctocogene roxaparvovec (valrox) In January 2022, the company announced full data from the Phase 3 clinical study GENEr8-1 of valrox, with 134 subjects achieving all primary and secondary outcomes in the two-year analysis To the efficacy endpoint
.

Designated primary analysis of Phase 3 clinical study GENEr8-1 on participants from a previous non-interventional study, all receiving a single 6e13vg/kg dose
.

The data showed that the annualized bleeding rate (ABR) was reduced by 85% from baseline, and the cumulative mean annualized bleeding rate (ABR) was less than 1
.

The EMA has previously accepted a Marketing Application (MAA) for this product candidate for adults with severe hemophilia
A.

In March 2021, the FDA granted valrox Regenerative Medicine Advanced Therapy Designation (RMAT)
.

Based on these results, BioMarin plans to resubmit its marketing application (BLA) to the FDA in the second quarter of 2022, followed by a six-month review by the FDA
.

Recommended reading: The first hemophilia gene therapy is about to hit the market? BioMarin Announces Phase 3 Data to Complete the Regulatory PuzzleRoche/Spark: SPK-8011 Transfer for Hemophilia A" Phase 1/2 clinical trial results, and the latest follow-up data for this product candidate will be announced at the ISTH2021 meeting
.

Of the 18 patients treated with SPK-8011, 16 maintained persistent factor VIII expression; the patients' annual bleeding rate (ABR) decreased by 91.
2% and the annual factor VIII infusion rate decreased by 97%
.

The company has another candidate gene therapy, SPK-8016, also targeting hemophilia A, which updated preliminary data from a Phase 1/2 clinical trial in February 2021
.

➤ ASC Therapeutics: ASC618 In July 2021, ASC Therapeutics announced that the FDA has approved the IND application for its investigational second-generation gene therapy ASC618 for the treatment of patients with severe or moderate hemophilia
A.

ASC618 is an AAV gene therapy that carries a codon-optimized B-domain-deleted factor VIII gene and a minimal-length, liver-specific promoter capable of endogenously producing factor VIII for the treatment of hemophilia
A.

In preclinical studies, ASC618 was able to produce sufficient factor VIII levels at doses significantly lower than other hemophilia A gene therapies
.

Recommended reading: Lower doses! U.
S.
FDA approves "high secretory" protein optimization strategy AAV gene therapy into clinical for the treatment of hemophilia AYimai Meng broke the news that other clinical candidates include Pfizer/Sangamo's giroctocogene fitelparvovec (SB-525), Bayer /Ultragenyx Pharmaceuticals' BAY2599023 (DTX201, AAVhu37 FVIII), Freeline's FLT210, Shire/Baxalta co-developed SHP654, etc.
, but no update progress has been announced recently
.

Nucleic Acid Drugs ➤ Novo Nordisk/2seventy: LNP-delivered mRNA in vivo therapeuticsIn January 2022, Bluebird spinoff 2seventy announced an expanded collaboration agreement with Novo Nordisk to deliver 2seventy bio's proprietary mRNA-based megaTAL™ technology to develop novel sustainable therapies targeting hemophilia
A.

2seventy bio's megaTAL technology has the potential to provide a highly specific and efficient way to "silence, edit or insert genetic components"
.

Recommended reading: Longer-lasting than AAV therapy? Novo Nordisk's US$40 million to further expand in vivo mRNA editing therapy for hemophiliaYimai Meng broke the news ➤ Sanofi/Alnylam: RNAi drug fitusiranIn December 2021, Sanofi announced the siRNA (small Positive data from a Phase 3 clinical trial of the interfering RNA) drug fitusiran
.

Fitusiran is a subcutaneously administered siRNA formulation that targets antithrombin, improves thrombin generation potential and rebalances hemostasis in hemophiliacs, and can be used in hemophilia A and B patients with or without inhibitors
.

Recommended reading: Subcutaneous siRNA drug breaks through again, Sanofi announces positive phase 3 data for hemophilia patientsYimai Meng reveals antibody drug ➤ Genentech: double anti-Hemlibra®In July 2021, Genentech recently announced that Hemlibra® ( The long-term follow-up data of the Phase 3b STASEY study of emicizumab-kxwh) in the treatment of advanced hemophilia A showed no new problems in its safety, and the ability to control bleeding remained consistent
.

Hemlibra, a bispecific monoclonal antibody targeting factor IXa and factor X, designed to replace the function of activated factor VIII, is approved in more than 100 countries for the treatment of A in the body containing a factor VIII inhibitor hemophilia
.

Recommended reading: Two-year follow-up data on double-antibody therapy for hemophilia A: safe and effectiveYimai Meng broke the news References: 1.
In the field of cell and gene therapy "New drug company founded by Rao Yi conducts clinical trial of AAV gene therapy for hemophilia 》2.
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