Innovassynth Technologies India Limited A knowledge based RD

Innovassynth Technologies (India) Limited ( A knowledge based - R&D Driven – ISO 9001 -2008 Chemical Service Company )

CORPORATE PROFILE

Promoted by Raheja Group and Ghia Group Both the groups have interest in different business segments Polyesters Batteries Construction Material Insurance Publication Software Chemicals Etc. Have partnership with large multinational companies across the world for many years

Infrastructure v Area of land : 65 Acres. v R&D Labs : 5 labs for 84 Chemists who can work on bench (2 for nucleosides, 2 for Organic Synthesis & 1 for nutraceuticals) v Kilo Lab : 3 No. (2 for Nucleosides & 1 for other Organic Synthesis) v Manufacturing Plants : 6 plants (including 2 exclusive plants for Nucleoside Products). v Exclusive Contract Manufacturing Plant for a European MNC v QC and Analytical method Development Lab v Effluent Treatment Plant

Nucleoside Capabilities

Innovassynth Advantages Ø 15 years of experience in supplying wide variety of Nucleoside products (including PNS, phosphoramidites, succinates and specialty products) Ø Working with large pharmaceutical MNCs, drug discovery companies and oligo manufacturing companies from the USA, Europe and Japan Ø Very large scale capacity (3000 kgs) to produce in-house PNS and phosphoramidites Ø Unique Capabilities and Extensive experience of Large Scale Sugar as well as Nucleoside chemistry as per customer requirements Ø Excellent track record of quality and timeline along with competitive pricing Ø Innovassynth has developed many critical reagents like DMT-Cl, Tac-Cl etc. in house. and currently manufacturing in very large scale

Innovassynth Phosphoramidite capacities (with standard and special protecting groups) Deoxy amidites: d. T, d. CAc/Bz, d. Gibu / tac / dmf, d. ABz / tac RNA Amidites (2’-O-TBDMS): U, CAc , Gibu, Abz 2’-OMe amidites: U, CAc / Bz, Gibu , ABz 2’-Fluoro amidites: U, CAc / Bz, Gibu, ABz We also offer PNS & Succinates of all the nucleoside products

Innovassynth Nucleoside Products Ø c. Et, LNA, ENA, L-RNA Nucleosides, Amidites and succinates (for license holders) Ø Succinates of all protected Nucleosides and Unylinker Ø Morpholino chlorophosphoramidates Ø ENA and UNA Phosphoramidites Ø Linker phosphoramidites (Biotin, 6 -aminohexyl, etc. ) Ø 5 -Bromo, 5 -Iodo uridine/deoxyuridine, 4 -Thio pyrimidine Nucleosides Ø Modified Sugar products starting from D-Glucose Ø Custom made products including some of the proprietary products which we supply only to the original inventor or their license holders We are working with drug discovery and pharmaceutical companies developing drugs using novel technology platforms like Antisense, Si. RNA, Micro-RNA, Apatamers, Speigelmers etc.

Deoxynucleoside products (PNS, Phosphoramidites & Succinates) Large Scale Production capabilities of deoxyamidites (50 kg batches for PNS and 25 kg batches for amidites) Efficient conversion of PNS to Phosphoramidites without column chromatography Amidites qualified and approved by leading drug discovery, pharma and oligo houses In-house production of N-Acetyl d. C PNS and Amidite Multi-kilo scale synthesis of Succinates

RNA Products (PNS, amidites & succinates) o Synthesis and scale up (Multi-kilo level) of 2’-OTBDMS RNA PNS, amidites & succinates o Modifications Developed: n CAc , G dmf, Apiv, n 2’-CPep, n 2’–Dithiomethyl protected amidite (exclusively for an European customer) o Advantages of our Synthetic Approach: n results in exclusive 2’-isomer n di. TBS intermediate allow crystallization

2’-O-Methyl Products (PNS, amidites & Succinates) o Synthesis and scale up of PNS, amidites & succinates (Multi-kilo level) o Advantages of our Synthetic Approach: n results in exclusive 2’-isomer n di. TBS intermediate allow crystallization n Conversion of U to C to avoid problems of 2’-alkylation of C

2’-Fluoro products (PNS, amidites & Succinates) Highlights q Developed efficient and scalable processes for manufacture of 2’-Fluoro PNS, amidites & Succinates q Production of kilo-level amidites without any chromatography q 2’-Fluoro products qualified, approved and supplied to leading pharma, drug discovery and oligo houses 2’-Fluoro column

2’-MOE Products ** (PNS, amidites & Succinates) Large scale producer for all 2’-MOE products (PNS, amidites & succinates) MOE-pyrimidines PNS produced at 100 kg lot Developed & scaled up efficient processes for MOE- purines B = Abz, T, Gi. Bu, 5 -Me-CBz R = H / CEPA / Succinate –TEA salt MOE products qualified, approved and supplied regularly to leading pharma, drug discovery and oligo houses We are in the supply chain of large pharma company whose product is already approved by USFDA ** For License Holders

c. Et chemistry at Innovassynth ** § Multi-kilo scale synthesis of all six c. Et monomer products (A, G, U, C, T & 5 -Me-C) § Very large scale synthesis of Nap. Mesylate sugar (50 kg/batch) § Convergent approach allows use of Nap. Mesyl sugar for producing all c. Et monomers § Excellent manufacturing set-up to carry out large scale glycosylation reactions § Consistent and reliable supplier of c. Et amidites § Working since 2009 for development, scale up and optimization of c. Et amidite manufacture ** For License Holders

LNA chemistry at Innovassynth ** Highlights v Synthesis of all four LNA monomers v Multi-Kilo scale synthesis of Bis. Mesylate sugar v Excellent manufacturing set-up to carry out large scale glycosylation reactions v Very Large scale synthesis of key intermediates: Allofuranose & Bis Mesyl sugar ** For License Holders

Morpholino chlorophosphoramidates ** Highlights v Synthesis of all four chlorophosphoroamidate activated morpholino subunits v In house preparation of good quality phosphorodichloridate reagent v All the morpholino chlorophosphoramidates approved by license holder pharma company ** For License Holders

Process Capabilities- Carbohydrate Chemistry v Carbohydrate Chemistry § Developed 4 sugar monomers and produced on 50 kg scale. § Multistep synthesis starting from D-Glucose into a trisaccharide intermediate for generic API was achieved § Also developed large scale synthesis of many specialty Nucleosides from the respective sugars (made from D-Glucose) and glycosylating them with appropriate heterocyclic bases to prepare various Constrained Bicyclic Nucleosides (LNA, c. Et, ENA)

Small Molecules Capabilities

Process Capabilities - Small Molecules v Grignard reactions § Handling reactions on large scale involving 100 s of kgs of Mg § Safety system to take care of handling of Grignards are developed v Friedel-crafts reaction § Handling large quantities of Al. Cl 3 for this reaction § The acidic effluent is disposed in very safe and unique manner (It is used by large common effluent treatment plants in Industrial areas as a substitute to alum for coagulation) v Boron Chemistry (Borates, Boronic Acids, Boron Mediated Asymmetric Synthesis) § Developed processes for many boronic acids by cheaper methods

Process Capabilities – Small Molecules v Cyanation (Na. CN, KCN, Cu. CN) § Developed complete facility for this reaction including handling, charging and disposal of effluent after destruction of cyanide residue § Special precaution is taken while handling the cyanide and people are provided with all safety gadgets and training v Halogenation (Aliphatic/Aromatic) § This includes both liquid bromine handling as well as chlorine gas handling from big toners of 1 MT v Catalytic Hydrogenation 30 Bar; 1500 C § We handle all types of catalysts § The noble metal catalysts are collected after use and sent for recovery

Process Capabilities- Small Molecules v Organometallic reactions § Developed skills to handle n. Bu. Li in big cylinders of capacity 400 kg § Full safety systems are developed for reactions involving n. Bu. Li § Optimized and scaled up processes for making Organometalic catalysts like zirconium complexes. v Oxidations using Metal Oxides, H 2 O 2, Per Acids, Hypochlorite v Reductions Using Metal Hydrides, Nobel Metals, Ni, Na/ Et. OH, Al Isopropoxide, Chemical Reductions v Aromatic Fluorination, Sulphonation

Few examples of our process strength and scale up capability: Sodium-β-glycerophosphate (g 2 p) § Process development and scale up to ton level in 6 months § Higher capacity was achieved in existing facility by improving process parameters § Since this product is used in Pharma foarmulations and in cell cultures, it has a very high worldwide demand. Isosulphan Blue § This is a dye used in diagnostics for cancer detection. § The chemistry involves handling of hazardous reagents like 65% oleum, dichromate solution, etc. § The purification process involves separating the product from inorganic salts. § Received US patent for the process for this product.

7 -Bromoheptene: § This is an intermediate for a Hep C drug in clinical trial Phase III § The product is manufactured regularly as per customer requirement in ton lot quantity. § The reaction involves Grignard reaction. Metallocine § This is a high end catalyst § Large scale reactions were carried out using 400 kg cylinders n-Bu. Li § Used in Polymerizations § Developed and scaled up for an international company