YBL NEWSLETTER Volume 8, Issue 1, June 2020

Yashraj Biotechnology Limited C-232 TTC Industrial Area, Pawane MIDC, Navi Mumbai 400705, India Website: www.yashraj.com Email: info@yashraj.com Telephone: +91 22 62166800

INSIDE THIS ISSUE • Mission 2024 • Covid-19 Serological

testing • Covid-19 Recombinant

Antigens • YBL Product Basket

details • Covid-19 Presumptive

testing • Contact Details

ADVISORY BOARD • Mr. Arvind Bhanushali • Mr. Bharat Dagha • Prof. G. Padmanaban • Dr. Paresh Bhanushali

EDITORIAL BOARD • Dr. Chander P. Puri Chief Editor

MEMBERS • Dr Shweta Bhatt • Dr. Gauri Awasthi • Dr. Anuj Kumar Gupta • Dr. Kunal Shukla • Dr. Mukesh M Tripathi • Mrs. Prerana Rathod • Mr. Nikhil Rautela • Dr. Anjali Karande

www.yashraj.com 1

YBL Launches Mission 2024 Yashraj Biotechnology Ltd. (YBL) has through its multitude growth and expansions, since inception in 1999, become one of the top 10 biotechnology firms in India (Silicon India 2019). To further expand and mark a leading presence in the global diagnostic sector we have embarked on a mission to strengthen our capacities and product portfolio and take concerted steps for it to translate into an appreciable business growth with meaningful societal impact by year 2024.

We are an ISO 13485:2016, ISO 9001:2015 and OHSAS 18001:2007 certified organization that has developed nearly 100 high quality biomarker antigen products, within the native and recombinant realms, as well as monoclonal antibodies that enable top global players in the diagnostic industry to make affordable diagnostics for Cancer, Cardiovascular, Neurological, Autoimmune, Inflammatory and Infectious diseases available to common man, in alignment with our company’s vision.

We have launched the Mission 2024 with an objective to not only augment our capacities to manufacture reagents for the diagnostic industry, such as native, recombinant and cell-derived antigens as well as monoclonal and polyclonal antibodies, but also to diversify into related areas to harness the best that biotechnology has to offer, in alignment with our company’s overall mission.

To realize Mission 2024, we will: (1) Enrich our human biomarker antigen product portfolio by adding products with unmet need and thus increasing market demand; (2) Contract manufacture tailor-made antigen and antibody products as per customer need and specifications; (3) Manufacture antigens for veterinary diagnostics; (4) Develop growth factors and enzymes for cell-culture and industrial applications; (5) Develop and use recombinant antibody library through phage display technology for the discovery and production of humanized recombinant antibodies in a faster and cost-effective manner for in vitro diagnostics as well as research and development; and (6) Develop and use stem cell technologies for preclinical drug discovery and screening, bio-banking, disease modelling as well as regenerative medicine. We have already developed several products using Stem Cell technologies and plan to further expand this portfolio going forward (For details, please visit www.yashraj.com).

2

COVID-19 (SARS-CoV-2) Research and Development

Considering pandemic situation of COVID-19 coronavirus SARS-CoV-2 (COVID-19) and urgent requirement of diagnostic reagent and platform, as mentioned below we have given priority to this work to cater to the needs of industries and academic institutions globally.

Recombinant COVID-19 proteins: Important proteins of COVID-19 coronavirus SARS-CoV-2 (COVID-19) including Spike S1 (Containing RBD), Spike S2, Nucleocapsid protein, Envelop protein and membrane protein are being developed using bacterial and mammalian expression systems.

Anti-IgG/IgM rapid test for COVID-19: The serological test to detect Anti-IgG/IgM antibodies developed against COVID-19 infection under development. This advantages of this test being: Highly stable sample: The immunoglobulin’s are highly stable making it good candidate for collection, transport, storage and testing than RNA from nasopharageal swab which is highly susceptible for degradation; Ease of collection: A simple finger-tip prick is enough for sample collection and unlike virus in nasopharyngeal, the antibodies are uniformly distributed through the blood; Point of care: The antibody test can be performed bed side of the patients with minimum training and without major instruments.

RT-qPCR test for COVID-19 and SARS: We have also initiated developing qualitative RT PCR kit for COVID-19, for use in public health laboratory settings without having virus material available. COVID-19 qualitative PCR is an in vitro RT-PCR assay for qualitative detection of 2019- Novel Corona Virus (2019-n COV) in respiratory specimen or sera. The 2019-n COV primer and probes sets designed on the basis of universal detection of SARS like coronavirus and for specific detection of 2019-n COV using E gene for screening whereas RdRP gene and N gene for confirmation based on Berlin Protocol version 2 and Article in Euro surveillance “Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR”. In single go it can detect covid-19 infection and differentiate it from SARS.

In line with our Mission 2024 objectives, we have initiated development of state-of-the-art infrastructure; Research, Development and Production-related activities are being expanded in over 100,000 sq. ft. of newly constructed facilities; and cGMP facility is being commissioned to manufacture clinical grade products for use in regenerative medicine. Technical strength of the staff is being augmented through induction of new talent and capacity building. From the current 200+ employees, by 2024 we endeavour to become a 500+ employee strong organization and further expand our business in relatively newer territories namely, S. Korea, Japan and yet unexplored areas of Europe and America where YBL commands a good business presence already. The Mission 2024 will also entail expansion and diversification through mergers and acquisitions of companies with business synergies through both vertical and horizontal merger mechanisms.

Most importantly, through these endeavours and new initiatives our focus would be to cater to customer requirements in terms of Uniqueness, Quality, Characterization, Validation of Application, for customized product delivery in a time bound manner.

We are very hopeful that Mission 2024 will strategically align our resources and capabilities to accomplish the broader Mission of our Company “Mission to achieve excellence in Biotechnology and utilize its power for the good of humanity, and ensure that the corporate objectives are met”.

Continued… YBL Launches Mission 2024

3 www.yashraj.com

High Quality Recombinant Antibodies developed using Synthetic Single Domain Antibody Phage Display Library

We have ventured into recombinant monoclonal antibody development and manufacturing for which synthetic Camelid single domain antibody (also referred as VHH or Nanobody) phage display library is being developed by us. It would offer quick, efficient and cost effective customized antibody discovery and manufacturing services to our esteemed customers.

High quality synthetic library is being engineered on stable, soluble scaffold, capable of accommodating diverse CDR mutagenesis. Being a naive library, this technology does not require use of animals for immunization purposes. This helps to save animals, and also makes antibody production possible for non-immunogenic, toxic or conserved proteins.. The amino acid sequences of the CDRs are diversified using preassembled trinucleotide building blocks referred as trinucleotide mutagenesis (TRIM) technology. In this way, we could achieve complete customization of the amino acid composition at randomized sites and avoid the occurrence of unwanted stop codons or amino acids. The prepared library will have variable CDR3 lengths with at least 1010 independent variants, as a result our library would be of significantly higher quality than by using conventional technologies.

Turnover time - Starting with purified target antigen, high quality antibodies would be made available within 8-10 weeks, and at least three unique binders against the target antigen.

Antibody product format- Based on desired application, we will provide enzyme, fluorophore or biotin conjugated Nanobody, as a bi-specific antibody targeting two different antigens or as a full-length antibody fused with either mouse, rabbit or human Fc region

YBL is well recognized leader to provide diagnostic antigens and antibodies, and with this advanced synthetic nanobody phage display library technology, we can provide the high quality antibodies according to customer’s demand in shortest possible time.

Controlled Randomization

4

Native antigens, used as diagnostic marker for various diseases, are purified from diverse human biomedical fluids and tissues. To support such activities the Company has (1) regulatory approvals from Government of India; (2) approvals from Clinical Ethics Committee for research on Human Subjects; (3) Pollution Control Boards of the States; (4) vast network for sourcing biomedical fluids; including but not limited to urine, plasma, seminal fluid, placenta, ascetic fluid, pleural fluid etc. from wide-range of national and international hospitals and healthcare providers; (5) state-of-the-art research and development facilities; (5) stringent quality control programs and quality assurance certification; and (6) highly competent technical and supporting staff.

Sourcing of human biomedical fluids, production and supply chain as well as product integrity are monitored through rigorous examinations and follow-up surveillance so that safety and quality are non-negotiable. R & D and product development is approved by the Department of Science and Industrial Research, Ministry of Science and Technology, Government of India.

Today YBL offers about 50, part pure and high pure, high quality disease-specific native biomarkers for Cancer, Cardiovascular, Neurological, Autoimmune, Inflammatory and Infectious diseases to leading global in vitro diagnostic companies.

Recombinant Antigens Developed By YBL Our Company has pioneered in the large scale production of recombinant proteins, with and without tags, through multiple systems such as bacteria, yeast, insect and mammalian expression and created unprecedented opportunities for need-based product customizations. Most of our recombinant proteins mimic native antigens and provide comparable reliability in in vitro diagnostic kits including their use as Controls and Immunogens by diagnostic industry.

Over 30 recombinant proteins are offered by our Company. Sophisticated research and development facilities and highly competent scientific staff ensure an efficient process development including but not limited to, identification of the gene encoding the protein of interest as well as the most compatible and high efficiency vector and expression system for gene cloning, expression and protein production along with augmentation to optimize highest protein titters. This is followed by a complex process design to enable large production of high purity recombinant protein of interest.

YBL also offer need-based customizations and development of recombinant proteins, enzymes, mutant forms of proteins and/or tagged versions of the same proteins through an efficient process development while offering most competitive pricing and some of the shortest lead times in the industry. We are also active in working on OEM assignments for protein purification, fast track feasibility studies and customization of biomarkers to enhance their function and stability.

Native Antigens Developed By YBL

Monoclonal Antibodies Developed By YBL

YBL have had the expertise to make mouse monoclonal antibodies (mabs) since the last fifteen years. We have an established Mouse hybridoma lab and mabs are produced for in-house use as well as for commercial sales . These mabs are extensively characterised and also validated by third party validation agencies certifying our quality and purity. We also have identified match-pair mabs that can be utilised for antigen quantification. More recently we propose to offer customised services to customers for making mabs to antigens of interest.

5

S.no Product name Source NATIVE ANTIGENS-RENAL MARKERS

1 Alpha-1-Microglobulin (A1M) Human Urine

2 β2 Microglobulin (B2M) Human Urine

3 Retinol Binding Protein (RBP) Human Urine

4 Neutrophil Gelatinase Associated Lipocalin (NGAL) Human Neutrophils

5 Cystatin-C (Part pure) Human Urine

NATIVE ANTIGENS-CANCER MARKERS

6 CA 15-3 (Breast Cancer Marker) Human Fluids

7 CA 125 (Ovarian Cancer Marker) Human Fluids

8 CA 72-4 (Pancreatic/Ovarian Cancer Marker) Human Fluids

9 CA 19-9 (Pancreatic/Gastrointestinal Marker) Human Fluids

10 Alpha-Feto Protein (AFP) Human Cord Blood

11 Carcino Embryonic Antigen (CEA) Human Cancer Fluids

12 Human Epididymis Protein 4 (HE4) Human Cancer Fluids

13 Kappa Free light chain (KFLC) Human Urine

14 Lambda Free Light Chain (LFLC) Human Urine

15 Prostrate-Specific Antigen (PSA) Human Seminal Plasma

16 Prostate-Specific Antigen-α1-Anti-Chymotrypsin Complex (PSA-Complex) PSA-ACT

Human Seminal and Blood Plasma

NATIVE ANTIGENS-INFECTION MARKERS

17 Hepatitis antigen Ad Subtype (HBsAg-Ad) Human Blood

18 Hepatitis antigen Ay Subtype (HBsAg-Ay) Human Blood

NATIVE ANTIGENS-INFLAMMATORY MARKERS

19 C-Reactive Protein (CRP) Human Fluids

20 D-Dimer Human Plasma

21 Human Azurocidin Human Neutrophils

22 Calprotectin Human Neutrophils

NATIVE ANTIGENS-OTHERS

23 Human Ferritin Human Placenta

24 Soluble Transferrin Receptor (sTfR) Human Plasma

25 Transferrin (unsaturated) Human Plasma

26 Transferrin (iron rich) Human Plasma

27 Transferrin (Iron rich Lyo) Human Plasma

28 Transferrin (Unsaturated Lyo) Human Plasma

29 Plasmatic Control Human Plasma

NATIVE ANTIGENS-PREGNANCY/CARDIAC MARKER

30 Pregnancy Associated Plasma Protein A (PAPPA) Human Placental Serum

NATIVE ANTIGENS-AUTO-IMMUNE MARKERS

31 Myeloperoxidase (MPO) Human Neutrophils

Our Product Basket: Native Antigens

www.yashraj.com

6

Our Product Basket: Recombinant Antigens S.no Product name Source

RECOMBINANT-CARDIAC MARKERS

1 Recombinant C-Reactive Protein (rCRP) Mammalian cells

2 Recombinant Galectin-3 E. coli

3 Recombinant Human Fatty Acid Binding Protein 3 (rFABP3) E. coli

4 Recombinant Troponin T E. coli

5 Recombinant Troponin I E. coli

6 Recombinant Creatine Kinase MM (rCKMM) E. coli

7 Recombinant Creatine Kinase MB (rCKMB) E. Coli

8 Recombinant NT-Pro BNP E. coli

9 Recombinant Pro BNP E. coli

RECOMBINANT-RENAL MARKERS

10 Recombinant Neutrophil Gelatinase Associated Lipocalin (rNGAL-mutant) E. coli

11 Recombinant Neutrophil Gelatinase Associated Lipocalin (rNGAL-wild) E. coli

RECOMBINANT-INFLAMMATORY MARKERS

12 Recombinant Human Serum Amyloid A (rSAA) E. coli

13 Recombinant IL-6 (rIL-6) E. coli

14 Recombinant IL-18 (rIL-18) E. coli

15 Recombinant Tumor Necrosis Factor (rTNFα) E. coli

RECOMBINANT-INFECTION MARKERS

16 Recombinant SLO E. coli

17 Recombinant SLO, Glutaraldehyde stabilized, contains free amino group E. coli

18 Recombinant SLO, Glutaraldehyde stabilized E. coli

19 Recombinant Beta 2 Defensin E. coli

20 Recombinant HIV-1 P24 E. coli

21 Recombinant Hepatitis B Core antigen E. coli

22 Recombinant Procalcitonin Lyophilised (without tag) E. coli

RECOMBINANT-OTHER MARKERS

23 Recombinant Prolactin (Lyophilized) E. coli

24 Recombinant Prolactin (liquid) E. coli

25 Recombinant Human Calprotectin (S100A8) Protein E. coli

26 Recombinant Human Calprotectin (S100A9) Protein E. coli

27 Recombinant Sex Hormone-Binding Globulin (SHBG) Mammalian cells

28 Recombinant Alpha-Synuclein (r α-Synuclein) E. coli

29 Recombinant Fibroblast Growth Factor 2 (FGF2) E. Coli

30 Recombinant-Neuron Specific Enolase (rNSE) E. coli

www.yashraj.com

Our Product Basket: Monoclonal Antibodies 1 CRP monoclonal antibody (CRP mAb) Mouse

2 CA 125 monoclonal antibody Mouse

3 PSA monoclonal antibody (PSA mAb) Mouse

Come and partner with us at Yashraj Biotechnology Limited in our quest to make diagnostics affordable and easily accessible!

For additional information and appointments please contact :

Mr. Bharat T. Dagha, Director, Business Development

bharat@yashrajbio.com; marketing@yashrajbio.com

ADDRESS YASHRAJ BIOTECHNOLOGY LTD.

C232, TTC Industrial Area, MIDC, Navi Mumbai 400705, Maharashtra, India. Phone No.: +91-22-6216 6800

YBL’s and its sister concern Aspira Diagnostics introduces ‘Blood Test for Covid-19 Presumptive Diagnosis’

7 www.yashraj.com

CONTACT DETAILS

During this pandemic, apart from the serological testings, we have also introduced ‘Blood test for Covid-19 Presumptive Diagnosis‘ in collaboration with our sister concern Aspira Pathlab & Diagnostics Ltd based in Mumbai. The presumptive testing includes a panel of following four parameters: a. Complete blood count (CBC) by flow cytometry: Decreased WBC count, lymphocytes & platelets have been

reported in more than 80% of Covid-19 positive patients. b. C-reactive protein (CRP): An increased value of CRP has been reported in 75-93% of COVID-19 positive

patients. c. Lactate dehydrogenase (LDH): An increase in LDH indicates that tissue may have been damaged or is

diseased and has been reported in more than 27- 92% of COVID-19 positive patients. d. Alanine transaminase(SGPT): Liver injury appears to be significantly more common among those with severe

infection. An increase in SGPT level has been reported in more than 25% of cases of COVID-19 positive patients.

The above four tests give a robust understanding of the possibility of COVID-19 suspicion which is further corroborated with our RT-PCR and Serological tests.