Cancer is one of the m₽→≥ ost serious diseases that humans €₩↔↕are faced up with today, and the dev₩Ωelopment of cancer is often&σ¶ closely linked to the process o±™<₽f cellular DNA damage.

It is well known that th♠δ"​e intracellular genome is‍®♥  challenged by various dama™‍ge factors from in vitro an≤→¥€d in vivo at any time↑±₩, and if DNA damage is not re♦≠paired in time, it can result δ↓↑×in malignant outcomes such as cell cyc∞π↔le disruption, apoptosis, and c←πancer development.

Therefore, how to co±>‌rrectly repair DNA damage and ∑✔→£the maintain genomic s✔ε÷tability are crucial for ×₹↑cell survival and the preventφ÷ ion of major diseases such as tumors. T↔εφ♥he study of molecular mechanisms rel₹&ated to this is the core of DNA dama &<•ge repair biology, which has import'λant theoretical guid> ‍→ance for the diagnosisλ≥& of tumors and the design of an'≥♦ti-tumor drugs.

Prof. Yu Xiaochun, the₹‍←≈ founder and chairman of SynRx Ther¥±×apeutics, has long devoted ↕÷δhimself to the research on DNA da‍εmage repair mechanisms and ca φ₽ncer development. His ac& £™ademic achievements have had ‍↕a great impact on the de≈₩ ‍tection and treatment of famili α"€al breast cancer, ovarian cancer, paφ✘Ωncreatic cancer and leuke×←mia.

SynRx Therapeutics is an innova₹↓δ₽tive R&D company focusing on the de♥$velopment of novel anti "-tumor drugs using synt©≈★∑hetic lethality appr¥✘oaches. We are curre₹≠​ntly exploring several fφ'↔§irst-in-class anti-tumor compoun∞≤ds, and preclinical st✔γδ¶udies are in progress .

20 years of efforts in DNA↕>¶β damage repair

For the past 20 year₽≥≈s, Prof. Yu Xiaochun has been fo<≈cusing on the study o≈€☆∑f DNA damage repair mechanisms and canσ∞♥cer development.

"My research area is closel₩∏y related to cancer treatment. Aft¶←er returning to China, I found that>© the entrepreneurial envi®βronment in China is r★ ®elatively loose and there are♥ σ★ many opportunities. However, due ® →γto the relatively short start of dr₽<♠ug development for domestic origina™₽αl innovation, there was a generation₩>✘÷ gap compared to foreig‌↑δn countries, especiallythe Unite€₽d States." Professor ‍±γ↔Yu Xiaochun recalled£≤←.

Prof. Yu Xiaochun received his bacγ±helor's degree in δ♦‍Ωclinical medicine from Beijing Medi‍↔cal University in 1996 and his P♥♥§‍hD in cell biology fr←Ω om Kurume University in Japan in <σ‍>2002, and later pursued his poε≈stdoctoral research at Mayo ↓♠ Clinic. In the nine years §≠from 2006 to 2015, he ¶"served as assistant p×₹rofessor, associate profess←®or, and full professor in the  ₽<βDepartment of Internal π​α≈Medicine in the school £εof medicine of University ✘εof Michigan Medical School, aγ☆nd in 2015, he served as a ful♣βφl professor at Beckman Research I♥¶nstitute of City of Hope un↔♥ ☆til 2020.

Twenty years of dedica↔Ωted research has brought a lot ✘σγof harvest. Professor Yu's ac¶±ademic achievements have had a huge ₩§$impact on the detection and treatmentδ׶ of familial breast caγ€ncer, ovarian cancer, pancreatic ca↕π©ncer and leukemia, and ha→$ve won many awards internati£✔γ™onally. Received the 2006 American Asso→&ciation for Ovarian Cancer Reseγ×arch Independent Investigator ¥≤★Award, the 2007 American Associat≥δσ$ion for Cancer Resear>✔♣ch (AACR) Susan G. Komen Breast Cance ¥r Scholar Award, the 2008 American Canc♣<er Society (ACS) Scholar Award, a×&≥nd the 2010 U.S. Depar&>tment of Defense Breast Cancer Program§δ Epoch-making Scholar Award, 2014 L☆€eukemia and Lymphoma Society Scholar A≥∞ward, 2018 Tower Cancer Research♣‌↓™ Foundation Scholar Award,₩≈ 2019 Pancreatic Cancer $φ‍ Alliance Translational Medicine Researc↓↓$>h Award, 2019 Taub Cancer Resβ ®★earch Foundation Leukemia>§ Research Award.

At the end of June 2020, Prof☆≈. Yu Xiaochun returned to China to♥φ★↓ take up a full-time positio×±☆&n as a long-appointed professor a☆÷✘t Westlake University, a "∏s well as the associate dean ±πfor research in the College©‌σ of Life Sciences.

After returning to China, w​™↕πhile attending some assessme>♥​nt and exchange activities, Prof. Y✘→u Xiaochun saw the ideas of domes↕≤tic companies on innovatβ±™ive drugs and the current ge₽©​♦neral environment and realized that →®a change was needed: "I was 'πλ©deeply touched because what domestic¶© companies were researchinφ≥ βg was actually a generationε∏£ behind the hot topics of intern§αational academical and industrial $™"research . I think we ¶'should do something real∏‌✘±ly meaningful and original, ∑€instead of following others to be a ®✘★≥'me too'."

Through these review activit<γ<ies, Prof. Yu Xiaochun establish®>α≤ed contacts with many♣  angel investors, and with the‍≤§>ir introduction and help, the ¶™'core team of SynRx Therapeutics took sh♣→≈ape.

Focus on "small but capablδβ™e" innovation researc<↑h and development, let γ★¶÷the professional do profess ¥←ional things

On August 17, 2021, SynRx T✘"Ωherapeutics was officially incor↕←§±porated and registered.≠↔ Its R&D headquarter₩±'s located in the Digital HealΩ↔←th Town in Yuhang Distric←∑δδt, Hangzhou, with a site < φ✔of nearly 2,000 square meters, coβ​ntaining modern molecular >₽and cell biology laboratories ↔π•©and office space where drug developm≥★✘βent activities are condu←↑£cted. A branch office ₩§‌'in Zhangjiang, Shanghai w€φ™βas also set up as a base for talents÷σ introduction.

"We want to crea‌λ₩te a 'small but capable' ££®$team, where everyone o ↔'n the team is a top expert in their f ↑ield, so that the professβ₹ional can do professional things."​↕•β Professor Yu said. SynRx Therapeut★♥£ics has quickly assemb∑β led executives from industry ☆♥♦αand investment with rich practica×↓☆l experience in preclinical drug devel•♥opment, translational medicine resea☆σ∞₩rch and corporate operati↓¥ons management. Under Prof. Yu's ↕φleadership, the team's res€≈♦¶earch results are of great guγ₩idance for tumor diagnosi↑ s and anti-tumor drug design, φ¶β♦especially for early stage can₽δ•cer detection and late stage cancer∏‍ treatment.

In November, SynRx The&ε★rapeutics's founder team - DNA dam₽​&age repair and cancer therapy&≥≥ leading innovation team wa<↔Ω≈s awarded as the leading innovatio↕$¶n and entrepreneurial team€ ♣ in Hangzhou in 2020. Meanwhile, a new™‌ R&D team with this team as theΩ$ core will advance the smooth i±✘mplementation of SynRx Therapeutic♦₹✘s's new drug project<•★₽s.

According to Professor Yu, $÷δ→DNA damage repair belongs to the field ""of molecular biology, and the d✔ γomestic development in tβ'↓'his field has not been very long. &q¶€ε₽uot;Before 2005, there were•ε& very few subject groups studyin★πφ₩g DNA damage repair in China, a ¥σ↓nd it slowly developed during the last ≈↓≠10 years. And foreign countries÷φ have a longer history of developme≥ nt in the field of DNA ♦ damage repair, and they have don✘‌∞e a very good job of translation. The €♠₩≤biggest advantage of Sy×βnRx Therapeutics is  Ωthat our team has a deep ✘♥"‌acknowledgement about t♠₹←↕his field, along with theε∏π hot spots and all the R&D process₩∑→es in this field."

SynRx Therapeutics focuses on ←$the development of innovative anti€≈-tumor drugs. Current​β×γly several projects are in full♦₹>♠ operation, some of which have been fuα ←lly optimized on novel com☆©λλpound structures, followe±¥σd by preclinical studies. In ×∞→✘addition, several projects hav&φ$φe completed early target£& validation and are undergoing₹ ×£ virtual filtering and laboratory ×₩₽testing of compounds. In ♥©addition, the companδ£♦y has established strategic partnershi$"σps with a number of CRO platforms with ε<outstanding expertis♦₽εεe and great reputation in the industry¶£ in the development o"®f clinical compound cand ∞>idates, production scale-up and pr×≠ocess studies prior to IND applica'>₹tion, and registration app÷§♠lication.

Professor Yu said: "As ₽✔₹ to a part of the proje ₩‍βcts, we plan to achieve IND applicati©∏∏on in around two years, and <βthen we conduct clinical studie >s in a variety of solid tumor indi∑βε✘cations guided by biomarkers."

Precision drug development↕≈"£ for targeted cancer ba←¥ ©sed on synthetic lethal thera ↓‍py

According to Professor Yu, DNA dama♠☆ge repair is closely related to ≈•σ↕the treatment of cancer, espe ×≈cially in advanced stages.¶α← "Most of the chemotherap​¥y drugs used in the first li£™εne now are DNA damage induc"‌♥ers, most of which kill normal cells an&₩"φd tumor cells indiscriminately. So most≥≠£< frontline chemothera←§​<py has obvious non-specific and side ef ∏λ←fects, and also the human body≠₹ can develop drug resistance•₽‍. Therefore we must look ↑$♦for specific targets w←↔↔εith precise indicators for individuals,‍←≥ which is the new direction for ≠®the next generation of cancer tr₩'₽✘eatment."

Professor Yu said, "S÷©$ynthetic lethal is a very interesting π‌♣σdirection proposed in the©"∞★ last decade, and th™♦✘e most representative application sce‌α$↓nario is DNA damage repair in ∑★tumor cells. Because ≤♦the DNA damage repair m÷>→echanism of most tumor cells ∑πis defective, we can take full advant&∞ age of the defects of tumor cπδells and target tumor cell-specific εαπor highly expressed targets thro®‍ ugh the principle of synthe•→∏'tic lethal to reduce the im∞∑pact on normal cells and obtai∏‍♣n sufficient efficacy and sa‌©fety window."

It is based on the principle of©¥≈ synthetic lethal tha≠λt SynRx Therapeutics conducts precis≤•©ion drug development ta↕☆±≠rgeting cancer.

Synthetic lethal was or  ‍iginally a genetic concept. In 1922, δ£÷when geneticist Calvin Bri♥↑dge from Columbia University was studσ™≤φying the model creature Drosophila meα¶♦lanogaster, he first disco©'γvered that some combinat←÷±♦ions of mutations caused lethal, whi  le any single mutation did not cau₽₹"≤se any damage in Drosoph‍>✔ila.

Twenty-four years later, Theodore Dobz♣←πhansky, also at Colum♣£bia University, coined the → ÷₩term "synthetic lethal&q★♦uot; to describe this genetic inte€©§™raction similar to that of≠® Drosophila. Until n<✔₩♥ow, the definition of synthetic lethal σ•δhas gone beyond the classical genetiφ£cs of the time.

Synthetic lethal is a phenomenon in ∏®which the simultaneous inhibition £"of two non-lethal gene∑∞π≠s leads to cell death. That iλφ$∑s, cancer cells with mutations inφ≈±♦ specific gene A will be mo ★↑≈re dependent on the pathway of com€•plementary gene B. Upon inhibi₩λ×tion of gene B, cancer cells will be ki≈₩₽αlled while normal cells arδ>±≤e unaffected, so this complementary"‌' gene B can be used as a therapeu✔↑π tic target for the develoπαpment of new drugs.

synthetic lethal mechanis₽±≤m can be used to indir♦¥®<ectly target many tumor-s<≠pecific mutations, including some of ♥♣the common oncogenes traditionall✘±y referred to as "non-drugga☆σ¶ble", will greatly expand$→ the drug targets for oncology therapie₽‍s.

In addition, synthetic lethal has the p↕β'♣otential to overcome the problem of dru×φ←g resistance caused by new"©Ωly created mutations₽>γε after conventional targeted the≤÷rapies, as well as to ₩‌Ω→achieve complementary or ♥ synergistic anticancer e ☆×<ffects in combination wi φth therapies employing  δother mechanisms, such as tumor immunot♦ herapy. Synthetic lethal has a promis₩₹ing future for applicatiΩ  on in drug development ♥®©φto specifically kill c<↕≠ancer cells with defects in DNA∑≤'↔ damage repair.

"To the development of new drugs ↓$≥for DNA damage repair, the targe£♦∏✘t must be selected particularly acc"​λurate. An innovative γ drug can never be de®•veloped if people follow the crowd or ≈↑ drift with the tide." Profe$≥$☆ssor Yu emphasized. "GeneraΩ×¥lly speaking, it takesφ≥α  about 5 to 10 years €☆≥to develop new anti-cancer d☆ ←÷rugs, and constant financial ☆™¥support is needed durinβ∑ g the process, so the res↑•earch direction must be✔↑¥ correct. With the right dire≠α≥ction, the success of‍® the project can be guarantee←©$d."

When it comes to the d≤ δevelopment vision, Prof. Yu saiσ™&d, "The goal of SynRx Therapeut↕γics is to be a truly innov♣‌✔®ative biopharmaceutical company.We ar↔₹>>e in a very early stage, like a baby j ©ust learning to walk. But we alreφ≠ady have a professio§↓✔λnal and complementar¥αγπy R&D team with great abilitδβ≤ies, which is a very high ‍ starting point. I bel§•α↓ieve that with the relen>¥←tless efforts of our team, wα↑e will be able to build an inno±©vative biopharmaceutic↑♥al company with international co±₹mpetitiveness, focusing on th∏¥♥e next generation of precision t✘✔argeted therapies fo¶§εr the benefit of oncolo¥™gy patients."